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1
Calvin, James M., und Marvin K. Nakayama. „SIMULATION OF PROCESSES WITH MULTIPLE REGENERATION SEQUENCES“. Probability in the Engineering and Informational Sciences 14, Nr. 2 (April 2000): 179–201. http://dx.doi.org/10.1017/s0269964800142056.
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The classical regenerative method of simulation output analysis exploits the regenerative structure of a stochastic process to break up a path into independent and identically distributed cycles based on a single sequence of regeneration times. If a process is regenerative with respect to more than one sequence of regeneration times, the classical regenerative method does not exploit the additional structure, and the variance of the resulting estimator for certain performance measures (e.g., the time-average variance constant) can vary greatly, depending on the particular regeneration sequence chosen. In a previous article, we introduced an efficiency-improvement technique for regenerative simulation of processes having two sequences of regeneration times based on permuting regenerative cycles associated with the second sequence of regeneration points. In this article, we show how to exploit more than two regeneration sequences. In particular, for birth–death Markov chains, the regenerations associated with hitting times to each state can all be exploited. We present empirical results that show significant variance reductions in some cases, and the results seem to indicate that the permuted estimator for the time-average variance constant can have a variance that is independent of the primary regeneration sequence used to run the simulation.
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Li, Yan, Lungen Lu und Xiaobo Cai. „Liver Regeneration and Cell Transplantation for End-Stage Liver Disease“. Biomolecules 11, Nr. 12 (20.12.2021): 1907. http://dx.doi.org/10.3390/biom11121907.
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Liver transplantation is the only curative option for end-stage liver disease; however, the limitations of liver transplantation require further research into other alternatives. Considering that liver regeneration is prevalent in liver injury settings, regenerative medicine is suggested as a promising therapeutic strategy for end-stage liver disease. Upon the source of regenerating hepatocytes, liver regeneration could be divided into two categories: hepatocyte-driven liver regeneration (typical regeneration) and liver progenitor cell-driven liver regeneration (alternative regeneration). Due to the massive loss of hepatocytes, the alternative regeneration plays a vital role in end-stage liver disease. Advances in knowledge of liver regeneration and tissue engineering have accelerated the progress of regenerative medicine strategies for end-stage liver disease. In this article, we generally reviewed the recent findings and current knowledge of liver regeneration, mainly regarding aspects of the histological basis of regeneration, histogenesis and mechanisms of hepatocytes’ regeneration. In addition, this review provides an update on the regenerative medicine strategies for end-stage liver disease. We conclude that regenerative medicine is a promising therapeutic strategy for end-stage liver disease. However, further studies are still required.
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Paatela, Ellen, Dane Munson und Nobuaki Kikyo. „Circadian Regulation in Tissue Regeneration“. International Journal of Molecular Sciences 20, Nr. 9 (08.05.2019): 2263. http://dx.doi.org/10.3390/ijms20092263.
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Circadian rhythms regulate over 40% of protein-coding genes in at least one organ in the body through mechanisms tied to the central circadian clock and to cell-intrinsic auto-regulatory feedback loops. Distinct diurnal differences in regulation of regeneration have been found in several organs, including skin, intestinal, and hematopoietic systems. Each regenerating system contains a complex network of cell types with different circadian mechanisms contributing to regeneration. In this review, we elucidate circadian regeneration mechanisms in the three representative systems. We also suggest circadian regulation of global translational activity as an understudied global regulator of regenerative capacity. A more detailed understanding of the molecular mechanisms underlying circadian regulation of tissue regeneration would accelerate the development of new regenerative therapies.
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Davenport, R. J. „Regenerating Regeneration“. Science of Aging Knowledge Environment 2004, Nr. 35 (01.09.2004): ns6. http://dx.doi.org/10.1126/sageke.2004.35.ns6.
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Hoban, M., und P. Beresford. „Regenerating regeneration“. Community Development Journal 36, Nr. 4 (01.10.2001): 312–20. http://dx.doi.org/10.1093/cdj/36.4.312.
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6
Alibardi, Lorenzo. „Regeneration or Scarring Derive from Specific Evolutionary Environmental Adaptations of the Life Cycles in Different Animals“. Biology 12, Nr. 5 (17.05.2023): 733. http://dx.doi.org/10.3390/biology12050733.
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The ability to heal or even regenerate large injuries in different animals derives from the evolution of their specific life cycles during geological times. The present, new hypothesis tries to explain the distribution of organ regeneration among animals. Only invertebrates and vertebrates that include larval and intense metamorphic transformations can broadly regenerate as adults. Basically, regeneration competent animals are aquatic while terrestrial species have largely or completely lost most of the regeneration ability. Although genomes of terrestrial species still contain numerous genes that in aquatic species allow a broad regeneration (“regenerative genes”), the evolution of terrestrial species has variably modified the genetic networks linking these genes to the others that evolved during land adaptation, resulting in the inhibition of regeneration. Loss of regeneration took place by the elimination of intermediate larval phases and metamorphic transformations in the life cycles of land invertebrates and vertebrates. Once the evolution along a specific lineage generated species that could no longer regenerate, this outcome could not change anymore. It is therefore likely that what we learn from regenerative species will explain their mechanisms of regeneration but cannot or only partly be applied to non-regenerative species. Attempts to introduce “regenerative genes” in non-regenerative species most likely would disorder the entire genetic networks of the latter, determining death, teratomas and cancer. This awareness indicates the difficulty to introduce regenerative genes and their activation pathways in species that evolved genetic networks suppressing organ regeneration. Organ regeneration in non-regenerating animals such as humans should move to bio-engineering interventions in addition to “localized regenerative gene therapies” in order to replace lost tissues or organs.
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Bergamini, Giulia, Mohamad Ahmad, Marina Cocchi und Davide Malagoli. „A New Protocol of Computer-Assisted Image Analysis Highlights the Presence of Hemocytes in the Regenerating Cephalic Tentacles of Adult Pomacea canaliculata“. International Journal of Molecular Sciences 22, Nr. 9 (09.05.2021): 5023. http://dx.doi.org/10.3390/ijms22095023.
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In humans, injuries and diseases can result in irreversible tissue or organ loss. This well-known fact has prompted several basic studies on organisms capable of adult regeneration, such as amphibians, bony fish, and invertebrates. These studies have provided important biological information and helped to develop regenerative medicine therapies, but important gaps concerning the regulation of tissue and organ regeneration remain to be elucidated. To this aim, new models for studying regenerative biology could prove helpful. Here, the description of the cephalic tentacle regeneration in the adult of the freshwater snail Pomacea canaliculata is presented. In this invasive mollusk, the whole tentacle is reconstructed within 3 months. Regenerating epithelial, connective, muscular and neural components are already recognizable 72 h post-amputation (hpa). Only in the early phases of regeneration, several hemocytes are retrieved in the forming blastema. In view of quantifying the hemocytes retrieved in regenerating organs, granular hemocytes present in the tentacle blastema at 12 hpa were counted, with a new and specific computer-assisted image analysis protocol. Since it can be applied in absence of specific cell markers and after a common hematoxylin-eosin staining, this protocol could prove helpful to evidence and count the hemocytes interspersed among regenerating tissues, helping to unveil the role of immune-related cells in sensory organ regeneration.
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Batwa, Mohammed, Rand Bakhsh, Zainab Alghamdi, Khaled Ageely, Abdullah Alzahrani, Abdullah Alshahrani, Khalid Mujthil et al. „Regenerative Therapies in the Treatment of Periodontal Defects“. JOURNAL OF HEALTHCARE SCIENCES 03, Nr. 08 (2023): 254–60. http://dx.doi.org/10.52533/johs.2023.30802.
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Regenerative therapies in periodontics have shown great potential in restoring damaged periodontal tissues. Techniques such as guided tissue regeneration (GTR) and guided bone regeneration (GBR) have been effective in promoting the regeneration of periodontal ligament, cementum, and alveolar bone. These approaches create a conducive environment for cell repopulation and exclusion of non-osteogenic cells, leading to successful periodontal tissue regeneration. Tissue engineering approaches, utilizing stem cells, growth factors, and biomaterial scaffolds, have also shown promise in regenerating multiple periodontal tissues simultaneously. However, challenges such as membrane exposure and infection need to be addressed. Emerging regenerative techniques, including enamel matrix derivatives (EMDs), stem cell-based therapies, growth factor delivery systems, and gene therapies, offer innovative strategies for periodontal defect treatment. Optimization of delivery systems, refinement of biomaterials, and advancements in gene therapy and tissue-specific biomaterials may further enhance the regenerative capacity of periodontal tissues. Despite challenges, regenerative therapies have the potential to revolutionize periodontics and improve clinical outcomes by addressing the root cause of periodontal diseases and promoting long-lasting tissue regeneration.
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Maganur, Prabhadevi. „Dental Pulp Stem Cells in Regenerative Therapy“. TEXILA INTERNATIONAL JOURNAL OF ACADEMIC RESEARCH 10, Nr. 2 (28.04.2023): 70–77. http://dx.doi.org/10.21522/tijar.2014.10.02.art007.
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Stem cells, also known as progenitor/precursor cells, have the unique trait of self-renewal and multi-lineage differentiation. Dental stem cells (DSCs) are holding a pivotal role during recent times as they thrive as the cornerstone for the development of cell transplantation therapies that correct periodontal disorders and damaged dentin. DSCs are used therapeutically for different organ systems and numerous diseases, including neurological disorders, diabetes, liver disease, bone tissue engineering, and dentistry. In dentistry, the focus is on predominantly regenerating the pulp and damaged dentin, repairing perforations, and periodontal regenerations. Above all, whole tooth regeneration has been constantly under research. The next decade could be a crucial junction where huge leaps in stem cell-based regenerative therapies could become a reality with successful tissue engineering therapies this could be a biological alternative to synthetic materials that are in use currently. But dental stem cells have their share of challenges for which the research must happen effectively adhering to social responsibilities at all levels. Keywords: Stem cells, Regeneration, Regenerative therapy, SHED.
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Gupta, Samudra, Suman Dutta und Subhra Prakash Hui. „Regenerative Potential of Injured Spinal Cord in the Light of Epigenetic Regulation and Modulation“. Cells 12, Nr. 13 (22.06.2023): 1694. http://dx.doi.org/10.3390/cells12131694.
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A spinal cord injury is a form of physical harm imposed on the spinal cord that causes disability and, in many cases, leads to permanent mammalian paralysis, which causes a disastrous global issue. Because of its non-regenerative aspect, restoring the spinal cord’s role remains one of the most daunting tasks. By comparison, the remarkable regenerative ability of some regeneration-competent species, such as some Urodeles (Axolotl), Xenopus, and some teleost fishes, enables maximum functional recovery, even after complete spinal cord transection. During the last two decades of intensive research, significant progress has been made in understanding both regenerative cells’ origins and the molecular signaling mechanisms underlying the regeneration and reconstruction of damaged spinal cords in regenerating organisms and mammals, respectively. Epigenetic control has gradually moved into the center stage of this research field, which has been helped by comprehensive work demonstrating that DNA methylation, histone modifications, and microRNAs are important for the regeneration of the spinal cord. In this review, we concentrate primarily on providing a comparison of the epigenetic mechanisms in spinal cord injuries between non-regenerating and regenerating species. In addition, we further discuss the epigenetic mediators that underlie the development of a regeneration-permissive environment following injury in regeneration-competent animals and how such mediators may be implicated in optimizing treatment outcomes for spinal cord injurie in higher-order mammals. Finally, we briefly discuss the role of extracellular vesicles (EVs) in the context of spinal cord injury and their potential as targets for therapeutic intervention.
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Karra, Ravi, Anne K. Knecht, Kazu Kikuchi und Kenneth D. Poss. „Myocardial NF-κB activation is essential for zebrafish heart regeneration“. Proceedings of the National Academy of Sciences 112, Nr. 43 (15.10.2015): 13255–60. http://dx.doi.org/10.1073/pnas.1511209112.
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Heart regeneration offers a novel therapeutic strategy for heart failure. Unlike mammals, lower vertebrates such as zebrafish mount a strong regenerative response following cardiac injury. Heart regeneration in zebrafish occurs by cardiomyocyte proliferation and reactivation of a cardiac developmental program, as evidenced by induction of gata4 regulatory sequences in regenerating cardiomyocytes. Although many of the cellular determinants of heart regeneration have been elucidated, how injury triggers a regenerative program through dedifferentiation and epicardial activation is a critical outstanding question. Here, we show that NF-κB signaling is induced in cardiomyocytes following injury. Myocardial inhibition of NF-κB activity blocks heart regeneration with pleiotropic effects, decreasing both cardiomyocyte proliferation and epicardial responses. Activation of gata4 regulatory sequences is also prevented by NF-κB signaling antagonism, suggesting an underlying defect in cardiomyocyte dedifferentiation. Our results implicate NF-κB signaling as a key node between cardiac injury and tissue regeneration.
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Fröbisch, Nadia B., Constanze Bickelmann und Florian Witzmann. „Early evolution of limb regeneration in tetrapods: evidence from a 300-million-year-old amphibian“. Proceedings of the Royal Society B: Biological Sciences 281, Nr. 1794 (07.11.2014): 20141550. http://dx.doi.org/10.1098/rspb.2014.1550.
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Salamanders are the only tetrapods capable of fully regenerating their limbs throughout their entire lives. Much data on the underlying molecular mechanisms of limb regeneration have been gathered in recent years allowing for new comparative studies between salamanders and other tetrapods that lack this unique regenerative potential. By contrast, the evolution of animal regeneration just recently shifted back into focus, despite being highly relevant for research designs aiming to unravel the factors allowing for limb regeneration. We show that the 300-million-year-old temnospondyl amphibian Micromelerpeton , a distant relative of modern amphibians, was already capable of regenerating its limbs. A number of exceptionally well-preserved specimens from fossil deposits show a unique pattern and combination of abnormalities in their limbs that is distinctive of irregular regenerative activity in modern salamanders and does not occur as variants of normal limb development. This demonstrates that the capacity to regenerate limbs is not a derived feature of modern salamanders, but may be an ancient feature of non-amniote tetrapods and possibly even shared by all bony fish. The finding provides a new framework for understanding the evolution of regenerative capacity of paired appendages in vertebrates in the search for conserved versus derived molecular mechanisms of limb regeneration.
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King, Ryan S., und Phillip A. Newmark. „The cell biology of regeneration“. Journal of Cell Biology 196, Nr. 5 (05.03.2012): 553–62. http://dx.doi.org/10.1083/jcb.201105099.
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Regeneration of complex structures after injury requires dramatic changes in cellular behavior. Regenerating tissues initiate a program that includes diverse processes such as wound healing, cell death, dedifferentiation, and stem (or progenitor) cell proliferation; furthermore, newly regenerated tissues must integrate polarity and positional identity cues with preexisting body structures. Gene knockdown approaches and transgenesis-based lineage and functional analyses have been instrumental in deciphering various aspects of regenerative processes in diverse animal models for studying regeneration.
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Goulart, Camila Oliveira, Henrique Rocha Mendonça, Julia Teixeira Oliveira, Laura Maria Savoldi, Luiza dos Santos Heringer, Alexandre dos Santos Rodrigues, Roberto Paes-de-Carvalho und Ana Maria Blanco Martinez. „Repulsive Environment Attenuation during Adult Mouse Optic Nerve Regeneration“. Neural Plasticity 2018 (12.09.2018): 1–11. http://dx.doi.org/10.1155/2018/5851914.
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The regenerative capacity of CNS tracts has ever been a great hurdle to regenerative medicine. Although recent studies have described strategies to stimulate retinal ganglion cells (RGCs) to regenerate axons through the optic nerve, it still remains to be elucidated how these therapies modulate the inhibitory environment of CNS. Thus, the present work investigated the environmental content of the repulsive axon guidance cues, such as Sema3D and its receptors, myelin debris, and astrogliosis, within the regenerating optic nerve of mice submitted to intraocular inflammation + cAMP combined to conditional deletion of PTEN in RGC after optic nerve crush. We show here that treatment was able to promote axonal regeneration through the optic nerve and reach visual targets at twelve weeks after injury. The Regenerating group presented reduced MBP levels, increased microglia/macrophage number, and reduced astrocyte reactivity and CSPG content following optic nerve injury. In addition, Sema3D content and its receptors are reduced in the Regenerating group. Together, our results provide, for the first time, evidence that several regenerative repulsive signals are reduced in regenerating optic nerve fibers following a combined therapy. Therefore, the treatment used made the CNS microenvironment more permissive to regeneration.
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Wang, Wei, Chi-Kuo Hu, An Zeng, Dana Alegre, Deqing Hu, Kirsten Gotting, Augusto Ortega Granillo et al. „Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates“. Science 369, Nr. 6508 (03.09.2020): eaaz3090. http://dx.doi.org/10.1126/science.aaz3090.
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Vertebrates vary in their ability to regenerate, and the genetic mechanisms underlying such disparity remain elusive. Comparative epigenomic profiling and single-cell sequencing of two related teleost fish uncovered species-specific and evolutionarily conserved genomic responses to regeneration. The conserved response revealed several regeneration-responsive enhancers (RREs), including an element upstream to inhibin beta A (inhba), a known effector of vertebrate regeneration. This element activated expression in regenerating transgenic fish, and its genomic deletion perturbed caudal fin regeneration and abrogated cardiac regeneration altogether. The enhancer is present in mammals, shares functionally essential activator protein 1 (AP-1)–binding motifs, and responds to injury, but it cannot rescue regeneration in fish. This work suggests that changes in AP-1–enriched RREs are likely a crucial source of loss of regenerative capacities in vertebrates.
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Prentiss, Nancy K., Mary S. Tyler und David Dean. „A morphological and histological investigation of the regeneration in Myxicola infundibulum (Montagu, 1808) (Sabellida, Annelida)“. Journal of the Marine Biological Association of the United Kingdom 97, Nr. 5 (13.03.2017): 1155–65. http://dx.doi.org/10.1017/s0025315417000248.
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Anterior regeneration of the annelid polychaete, Myxicola infundibulum (Montagu, 1808) is described from histological and SEM perspectives. This article provides additional evidence that anterior and posterior regeneration of isolated worm pieces does occur in this species, but that regenerative ability is restricted to abdominal pieces obtained from small individuals (less than 5 mm in thorax diameter and 10–20 mm in length). New cartilage tissue forms within the regenerating crown, but thoracic regeneration is limited to three segments. Anterior and posterior regeneration occurred within isolated pieces excised from the abdomen, resulting in the formation of 13 clones, with up to five individuals per clone.
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Banerji, Christopher R. S., Don Henderson, Rabi N. Tawil und Peter S. Zammit. „Skeletal muscle regeneration in facioscapulohumeral muscular dystrophy is correlated with pathological severity“. Human Molecular Genetics 29, Nr. 16 (03.08.2020): 2746–60. http://dx.doi.org/10.1093/hmg/ddaa164.
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Abstract Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant myopathy characterized by slowly progressive skeletal muscle weakness and wasting. While a regenerative response is often provoked in many muscular dystrophies, little is known about whether a regenerative response is regularly elicited in FSHD muscle, prompting this study. For comparison, we also examined the similarly slowly progressing myotonic dystrophy type 2 (DM2). To first investigate regeneration at the transcriptomic level, we used the 200 human gene Hallmark Myogenesis list. This myogenesis biomarker was elevated in FSHD and control healthy myotubes compared to their myoblast counterparts, so is higher in myogenic differentiation. The myogenesis biomarker was also elevated in muscle biopsies from most independent FSHD, DM2 or Duchenne muscular dystrophy (DMD) studies compared to control biopsies, and on meta-analysis for each condition. In addition, the myogenesis biomarker was a robust binary discriminator of FSHD, DM2 and DMD from controls. We also analysed muscle regeneration at the protein level by immunolabelling muscle biopsies for developmental myosin heavy chain. Such immunolabelling revealed one or more regenerating myofibres in 76% of FSHD muscle biopsies from quadriceps and 91% from tibialis anterior. The mean proportion of regenerating myofibres per quadriceps biopsy was 0.48%, significantly less than 1.72% in the tibialis anterior. All DM2 muscle biopsies contained regenerating myofibres, with a mean of 1.24% per biopsy. Muscle regeneration in FSHD was correlated with the pathological hallmarks of fibre size variation, central nucleation, fibrosis and necrosis/regeneration/inflammation. In summary, the regenerative response in FSHD muscle biopsies correlates with the severity of pathology.
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Abidi, Syeda Nayab Fatima, Felicity Ting-Yu Hsu und Rachel K. Smith-Bolton. „Regenerative growth is constrained by brain tumor to ensure proper patterning in Drosophila“. PLOS Genetics 19, Nr. 12 (21.12.2023): e1011103. http://dx.doi.org/10.1371/journal.pgen.1011103.
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Some animals respond to injury by inducing new growth to regenerate the lost structures. This regenerative growth must be carefully controlled and constrained to prevent aberrant growth and to allow correct organization of the regenerating tissue. However, the factors that restrict regenerative growth have not been identified. Using a genetic ablation system in the Drosophila wing imaginal disc, we have identified one mechanism that constrains regenerative growth, impairment of which also leads to erroneous patterning of the final appendage. Regenerating discs with reduced levels of the RNA-regulator Brain tumor (Brat) exhibit enhanced regeneration, but produce adult wings with disrupted margins that are missing extensive tracts of sensory bristles. In these mutants, aberrantly high expression of the pro-growth factor Myc and its downstream targets likely contributes to this loss of cell-fate specification. Thus, Brat constrains the expression of pro-regeneration genes and ensures that the regenerating tissue forms the proper final structure.
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Dadgar, Sherry, Zuyi Wang, Helen Johnston, Akanchha Kesari, Kanneboyina Nagaraju, Yi-Wen Chen, D. Ashley Hill et al. „Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy“. Journal of Cell Biology 207, Nr. 1 (13.10.2014): 139–58. http://dx.doi.org/10.1083/jcb.201402079.
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We sought to determine the mechanisms underlying failure of muscle regeneration that is observed in dystrophic muscle through hypothesis generation using muscle profiling data (human dystrophy and murine regeneration). We found that transforming growth factor β–centered networks strongly associated with pathological fibrosis and failed regeneration were also induced during normal regeneration but at distinct time points. We hypothesized that asynchronously regenerating microenvironments are an underlying driver of fibrosis and failed regeneration. We validated this hypothesis using an experimental model of focal asynchronous bouts of muscle regeneration in wild-type (WT) mice. A chronic inflammatory state and reduced mitochondrial oxidative capacity are observed in bouts separated by 4 d, whereas a chronic profibrotic state was seen in bouts separated by 10 d. Treatment of asynchronously remodeling WT muscle with either prednisone or VBP15 mitigated the molecular phenotype. Our asynchronous regeneration model for pathological fibrosis and muscle wasting in the muscular dystrophies is likely generalizable to tissue failure in chronic inflammatory states in other regenerative tissues.
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Green, Eric M., und Richard T. Lee. „Proteins and Small Molecules for Cellular Regenerative Medicine“. Physiological Reviews 93, Nr. 1 (Januar 2013): 311–25. http://dx.doi.org/10.1152/physrev.00005.2012.
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Regenerative medicine seeks to understand tissue development and homeostasis and build on that knowledge to enhance regeneration of injured tissues. By replenishing lost functional tissues and cells, regenerative medicine could change the treatment paradigm for a broad range of degenerative and ischemic diseases. Multipotent cells hold promise as potential building blocks for regenerating lost tissues, but successful tissue regeneration will depend on comprehensive control of multipotent cells–differentiation into a target cell type, delivery to a desired tissue, and integration into a durable functional structure. At each step of this process, proteins and small molecules provide essential signals and, in some cases, may themselves act as effective therapies. Identifying these signals is thus a fundamental goal of regenerative medicine. In this review we discuss current progress using proteins and small molecules to regulate tissue regeneration, both in combination with cellular therapies and as monotherapy.
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Edgar, Allison, Dorothy G. Mitchell und Mark Q. Martindale. „Whole-Body Regeneration in the Lobate Ctenophore Mnemiopsis leidyi“. Genes 12, Nr. 6 (05.06.2021): 867. http://dx.doi.org/10.3390/genes12060867.
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Ctenophores (a.k.a. comb jellies) are one of the earliest branching extant metazoan phyla. Adult regenerative ability varies greatly within the group, with platyctenes undergoing both sexual and asexual reproduction by fission while others in the genus Beroe having completely lost the ability to replace missing body parts. We focus on the unique regenerative aspects of the lobate ctenophore, Mnemiopsis leidyi, which has become a popular model for its rapid wound healing and tissue replacement, optical clarity, and sequenced genome. M. leidyi’s highly mosaic, stereotyped development has been leveraged to reveal the polar coordinate system that directs whole-body regeneration as well as lineage restriction of replacement cells in various regenerating organs. Several cell signaling pathways known to function in regeneration in other animals are absent from the ctenophore’s genome. Further research will either reveal ancient principles of the regenerative process common to all animals or reveal novel solutions to the stability of cell fates and whole-body regeneration.
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Kami, Katsuya, und Emiko Senba. „In Vivo Activation of STAT3 Signaling in Satellite Cells and Myofibers in Regenerating Rat Skeletal Muscles“. Journal of Histochemistry & Cytochemistry 50, Nr. 12 (Dezember 2002): 1579–89. http://dx.doi.org/10.1177/002215540205001202.
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Although growth factors and cytokines play critical roles in skeletal muscle regeneration, intracellular signaling molecules that are activated by these factors in regenerating muscles have been not elucidated. Several lines of evidence suggest that leukemia inhibitory factor (LIF) is an important cytokine for the proliferation and survival of myoblasts in vitro and acceleration of skeletal muscle regeneration. To elucidate the role of LIF signaling in regenerative responses of skeletal muscles, we examined the spatial and temporal activation patterns of an LIF-associated signaling molecule, the signal transducer and activator transcription 3 (STAT3) proteins in regenerating rat skeletal muscles induced by crush injury. At the early stage of regeneration, activated STAT3 proteins were first detected in the nuclei of activated satellite cells and then continued to be activated in proliferating myoblasts expressing both PCNA and MyoD proteins. When muscle regeneration progressed, STAT3 signaling was no longer activated in differentiated myoblasts and myotubes. In addition, activation of STAT3 was also detected in myonuclei within intact sarcolemmas of surviving myofibers that did not show signs of necrosis. These findings suggest that activation of STAT3 signaling is an important molecular event that induces the successful regeneration of injured skeletal muscles.
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Melo-Narváez, M. Camila, John Stegmayr, Darcy E. Wagner und Mareike Lehmann. „Lung regeneration: implications of the diseased niche and ageing“. European Respiratory Review 29, Nr. 157 (30.09.2020): 200222. http://dx.doi.org/10.1183/16000617.0222-2020.
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Most chronic and acute lung diseases have no cure, leaving lung transplantation as the only option. Recent work has improved our understanding of the endogenous regenerative capacity of the lung and has helped identification of different progenitor cell populations, as well as exploration into inducing endogenous regeneration through pharmaceutical or biological therapies. Additionally, alternative approaches that aim at replacing lung progenitor cells and their progeny through cell therapy, or whole lung tissue through bioengineering approaches, have gained increasing attention. Although impressive progress has been made, efforts at regenerating functional lung tissue are still ineffective. Chronic and acute lung diseases are most prevalent in the elderly and alterations in progenitor cells with ageing, along with an increased inflammatory milieu, present major roadblocks for regeneration. Multiple cellular mechanisms, such as cellular senescence and mitochondrial dysfunction, are aberrantly regulated in the aged and diseased lung, which impairs regeneration. Existing as well as new human in vitro models are being developed, improved and adapted in order to study potential mechanisms of lung regeneration in different contexts. This review summarises recent advances in understanding endogenous as well as exogenous regeneration and the development of in vitro models for studying regenerative mechanisms.
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Guo, Biao, Baojian Wu, Feng Wen und Kun Qiu. „Cascaded Nonlinear-Optical Loop Mirror-Based All-Optical PAM Regenerator“. Applied Sciences 10, Nr. 1 (26.12.2019): 206. http://dx.doi.org/10.3390/app10010206.
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An all-optical regeneration scheme based on cascaded nonlinear-optical loop mirrors (NOLMs) for pulse amplitude modulation (PAM) signals is proposed. The optimal working point (WP) of every NOLM can be set by means of the normalized power transfer function (NPTF) and normalized differential gain (NDG). As examples, the PAM-4 and PAM-8 regenerations based on cascaded two-NOLMs are demonstrated by optimizing the splitting ratios of the optical couplers and the gain coefficient of the inter-stage matching amplifier, achieving the Q-factor improvements of 25.32dB and 21.18dB, respectively. Compared to the conventional regenerator scheme, a 1.69dB signal-to-noise ratio (SNR) gain is achieved due to the flat power response within the regenerative range.
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Masood, Nausheen, und Alessio Russo. „Community Perception of Brownfield Regeneration through Urban Rewilding“. Sustainability 15, Nr. 4 (20.02.2023): 3842. http://dx.doi.org/10.3390/su15043842.
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Brownfield regeneration using a rewilding approach could provide an opportunity to create new green spaces in our cities. However, studies on public perceptions of rewilding projects are limited. Thus, the purpose of this study was to better understand the public’s perspective of brownfield regeneration and the perceived advantages that these regenerations may give if regenerated as urban green areas as part of rewilding projects. An online survey containing 21 dichotomous and multiple-choice items was created to learn about people’s preferences for brownfield regeneration, the advantages of urban rewilding, and the value of biodiversity in urban contexts. Results show that most people are aware of the benefits of urban regeneration and receptive to the idea of rewilding for urban resilience. Our findings raise awareness of the possibility of regenerating abandoned lots to create accessible green spaces for our communities.
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Nakajima, Wataru, Soya Nakanishi, Ryosuke Hosoya, Toshiaki Uemoto, Shiro Ohgo und Naoyuki Wada. „Regenerative Polarity of the Fin Ray in Zebrafish Caudal Fin and Related Tissue Formation on the Cut Surface“. Journal of Developmental Biology 9, Nr. 4 (19.11.2021): 50. http://dx.doi.org/10.3390/jdb9040050.
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Zebrafish caudal fin rays are used as a model system for regeneration because of their high regenerative ability, but studies on the regeneration polarity of the fin ray are limited. To investigate this regeneration polarity, we made a hole to excise part of the fin ray and analyzed the regeneration process. We confirmed that the fin rays always regenerated from the proximal margin toward the distal margin, as previously reported; however, regeneration-related genes were expressed at both the proximal and distal edges of the hole in the early stage of regeneration, suggesting that the regenerative response also occurs at the distal edge. One difference between the proximal and distal margins is a sheet-like tissue that is formed on the apical side of the regenerated tissue at the proximal margin. This sheet-like tissue was not observed at the distal edge. To investigate whether the distal margin was also capable of forming this sheet-like tissue and subsequent regeneration, we kept the distal margin separated from the proximal margin by manipulation. Consequently, the sheet-like tissue was formed at the distal margin and regeneration of the fin ray was also induced. The regenerated fin rays from the distal margin protruded laterally from the caudal fin and then bent distally, and their ends showed the same characteristics as those of the normal fin rays. These results suggest that fin rays have an ability to regenerate in both directions; however, under normal conditions, regeneration is restricted to the proximal margin because the sheet-like tissue is preferentially formed on the apical side of the regenerating tissue from the proximal margin.
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Qin, Yiming, Nanxuan Zhao, Bin Sheng und Rynson W. H. Lau. „Text2City: One-Stage Text-Driven Urban Layout Regeneration“. Proceedings of the AAAI Conference on Artificial Intelligence 38, Nr. 5 (24.03.2024): 4578–86. http://dx.doi.org/10.1609/aaai.v38i5.28257.
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Regenerating urban layout is an essential process for urban regeneration. In this paper, we propose a new task called text-driven urban layout regeneration, which provides an intuitive input modal - text - for users to specify the regeneration, instead of designing complex rules. Given the target region to be regenerated, we propose a one-stage text-driven urban layout regeneration model, Text2City, to jointly and progressively regenerate the urban layout (i.e., road and building layouts) based on textual layout descriptions and surrounding context (i.e., urban layouts and functions of the surrounding regions). Text2City first extracts road and building attributes from the textual layout description to guide the regeneration. It includes a novel one-stage joint regenerator network based on the conditioned denoising diffusion probabilistic models (DDPMs) and prior knowledge exchange. To harmonize the regenerated layouts through joint optimization, we propose the interactive & enhanced guidance module for self-enhancement and prior knowledge exchange between road and building layouts during the regeneration. We also design a series of constraints from attribute-, geometry- and pixel-levels to ensure rational urban layout generation. To train our model, we build a large-scale dataset containing urban layouts and layout descriptions, covering 147K regions. Qualitative and quantitative evaluations show that our proposed method outperforms the baseline methods in regenerating desirable urban layouts that meet the textual descriptions.
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Zimowska, Małgorzata, Karolina Archacka, Edyta Brzoska, Joanna Bem, Areta M. Czerwinska, Iwona Grabowska, Paulina Kasprzycka et al. „IL-4 and SDF-1 Increase Adipose Tissue-Derived Stromal Cell Ability to Improve Rat Skeletal Muscle Regeneration“. International Journal of Molecular Sciences 21, Nr. 9 (07.05.2020): 3302. http://dx.doi.org/10.3390/ijms21093302.
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Skeletal muscle regeneration depends on the satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, these cells might not sufficiently support repair. Thus, other cell populations, among them adipose tissue-derived stromal cells (ADSCs), are tested as a tool to improve regeneration. Importantly, the pro-regenerative action of such cells could be improved by various factors. In the current study, we tested whether IL-4 and SDF-1 could improve the ability of ADSCs to support the regeneration of rat skeletal muscles. We compared their effect at properly regenerating fast-twitch EDL and poorly regenerating slow-twitch soleus. To this end, ADSCs subjected to IL-4 and SDF-1 were analyzed in vitro and also in vivo after their transplantation into injured muscles. We tested their proliferation rate, migration, expression of stem cell markers and myogenic factors, their ability to fuse with myoblasts, as well as their impact on the mass, structure and function of regenerating muscles. As a result, we showed that cytokine-pretreated ADSCs had a beneficial effect in the regeneration process. Their presence resulted in improved muscle structure and function, as well as decreased fibrosis development and a modulated immune response.
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Wang, S., X. L. Tan, J. P. Michaud, Z. K. Shi und F. Zhang. „Sexual selection drives the evolution of limb regeneration in Harmonia axyridis (Coleoptera: Coccinellidae)“. Bulletin of Entomological Research 105, Nr. 2 (30.01.2015): 245–52. http://dx.doi.org/10.1017/s0007485315000036.
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AbstractWhen Harmonia axyridis larvae were subjected to amputation of a foreleg in the fourth instar, 83% survived and, of these, 75% regenerated the leg during pupation. Regenerators pupated at heavier weights than controls (unoperated) or non-regenerators, and spent longer in pupation. Regenerated males were preferred by females in choice tests and produced more viable progeny than control males. Unregenerated males were less preferred by females, copulated for shorter periods than control males, and reduced female fecundity. Amputation diminished beneficial paternal effects, whether males regenerated or not, resulting in progeny with slower development and smaller adult body mass relative to control paternity. Progeny of unregenerated males had lower survival and body mass, whether male or female, confirming that regeneration was an honest signal of mate quality. When offspring had a foreleg amputated, a regenerated paternity yielded higher survival than control paternity, but similar rates of regeneration, whereas an unregenerated paternity yielded lower rates of survival and leg regeneration than control paternity. Regenerating beetles were twice as likely to be melanic as non-regenerating or control beetles, suggesting pleiotropic effects of melanism on processes involved in regeneration. This is the first report of complete limb regeneration by a holometabolous insect in the pupal stage, and the first example of sexual selection for regenerative capacity.
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Rahman, Fasih Ahmad, Sarah Anne Angus, Kyle Stokes, Phillip Karpowicz und Matthew Paul Krause. „Impaired ECM Remodeling and Macrophage Activity Define Necrosis and Regeneration Following Damage in Aged Skeletal Muscle“. International Journal of Molecular Sciences 21, Nr. 13 (27.06.2020): 4575. http://dx.doi.org/10.3390/ijms21134575.
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Regenerative capacity of skeletal muscle declines with age, the cause of which remains largely unknown. We investigated extracellular matrix (ECM) proteins and their regulators during early regeneration timepoints to define a link between aberrant ECM remodeling, and impaired aged muscle regeneration. The regeneration process was compared in young (three month old) and aged (18 month old) C56BL/6J mice at 3, 5, and 7 days following cardiotoxin-induced damage to the tibialis anterior muscle. Immunohistochemical analyses were performed to assess regenerative capacity, ECM remodeling, and the macrophage response in relation to plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), and ECM protein expression. The regeneration process was impaired in aged muscle. Greater intracellular and extramyocellular PAI-1 expression was found in aged muscle. Collagen I was found to accumulate in necrotic regions, while macrophage infiltration was delayed in regenerating regions of aged muscle. Young muscle expressed higher levels of MMP-9 early in the regeneration process that primarily colocalized with macrophages, but this expression was reduced in aged muscle. Our results indicate that ECM remodeling is impaired at early time points following muscle damage, likely a result of elevated expression of the major inhibitor of ECM breakdown, PAI-1, and consequent suppression of the macrophage, MMP-9, and myogenic responses.
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Shimono, M., T. Inoue und T. Yamamura. „Regeneration of Periodontal Tissues“. Advances in Dental Research 2, Nr. 2 (November 1988): 223–27. http://dx.doi.org/10.1177/08959374880020020501.
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To elucidate the regenerative capability of the periodontal tissues, we carried out two experiments: (1) Regeneration of the gingival tissue following gingivectomy in rats. Ultrastructurally, regenerating junctional epithelium was similar in morphology to that of untreated animals and appeared to attach to the enamel after five days. Basal lamina and hemidesmosomes were produced faster at the enamel interface than at the connective tissue interface. Gingival tissue was completely regenerated seven days after the gingivectomy. (2) Regeneration of the cementum, periodontal ligament, and alveolar bone following intradentinal cavity preparation in dogs. In the early stages, the cavity was filled with an exudate and granulation tissue. Seven days after the operation, osteoblasts and cementoblasts were arranged regularly on the cut surface of the alveolar bone and dentin, respectively. Newly formed bone and cementum, and periodontal ligament grew to resemble pre-existing bone and cementum after 28-42 days. From these results, it is suggested that the periodontal tissues have an extremely high capability of regeneration.
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Karra, Ravi, Matthew J. Foglia, Wen-Yee Choi, Christine Belliveau, Paige DeBenedittis und Kenneth D. Poss. „Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish“. Proceedings of the National Academy of Sciences 115, Nr. 35 (13.08.2018): 8805–10. http://dx.doi.org/10.1073/pnas.1722594115.
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During heart development and regeneration, coronary vascularization is tightly coupled with cardiac growth. Although inhibiting vascularization causes defects in the innate regenerative response of zebrafish to heart injury, angiogenic signals are not known to be sufficient for triggering regeneration events. Here, by using a transgenic reporter strain, we found that regulatory sequences of the angiogenic factor vegfaa are active in epicardial cells of uninjured animals, as well as in epicardial and endocardial tissue adjacent to regenerating muscle upon injury. Additionally, we find that induced cardiac overexpression of vegfaa in zebrafish results in overt hyperplastic thickening of the myocardial wall, accompanied by indicators of angiogenesis, epithelial-to-mesenchymal transition, and cardiomyocyte regeneration programs. Unexpectedly, vegfaa overexpression in the context of cardiac injury enabled ectopic cardiomyogenesis but inhibited regeneration at the site of the injury. Our findings identify Vegfa as one of a select few known factors sufficient to activate adult cardiomyogenesis, while also illustrating how instructive factors for heart regeneration require spatiotemporal control for efficacy.
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Grigoryan, Eleonora N. „Study of Natural Longlife Juvenility and Tissue Regeneration in Caudate Amphibians and Potential Application of Resulting Data in Biomedicine“. Journal of Developmental Biology 9, Nr. 1 (18.01.2021): 2. http://dx.doi.org/10.3390/jdb9010002.
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The review considers the molecular, cellular, organismal, and ontogenetic properties of Urodela that exhibit the highest regenerative abilities among tetrapods. The genome specifics and the expression of genes associated with cell plasticity are analyzed. The simplification of tissue structure is shown using the examples of the sensory retina and brain in mature Urodela. Cells of these and some other tissues are ready to initiate proliferation and manifest the plasticity of their phenotype as well as the correct integration into the pre-existing or de novo forming tissue structure. Without excluding other factors that determine regeneration, the pedomorphosis and juvenile properties, identified on different levels of Urodele amphibians, are assumed to be the main explanation for their high regenerative abilities. These properties, being fundamental for tissue regeneration, have been lost by amniotes. Experiments aimed at mammalian cell rejuvenation currently use various approaches. They include, in particular, methods that use secretomes from regenerating tissues of caudate amphibians and fish for inducing regenerative responses of cells. Such an approach, along with those developed on the basis of knowledge about the molecular and genetic nature and age dependence of regeneration, may become one more step in the development of regenerative medicine
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Schebesta, Michael, Ching-Ling Lien, Felix B. Engel und Mark T. Keating. „Transcriptional Profiling of Caudal Fin Regeneration in Zebrafish“. Scientific World JOURNAL 6 (2006): 38–54. http://dx.doi.org/10.1100/tsw.2006.326.
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Regeneration of severed limbs in adult animals is restricted to urodele amphibians. Mammals, including humans, have very limited regenerative capabilities and even with proper treatment, only the tips of our digits can grow back. Teleost fish can regenerate amputated fins, the evolutionary ancestors of limbs. To elucidate the principles of limb-fin regeneration, we performed an Affymetrix microarray screen on regenerating caudal fins 12, 24, 48, and 72 h post amputation. Approximately 15,000 zebrafish transcripts were analyzed, identifying 829 transcripts as differentially expressed during regeneration. Of those, 563 were up-regulated and 266 were down-regulated. We constructed a comprehensive database containing expression data, functional assignment, and background information from the literature for each differentially expressed transcript. In order to validate our findings, we employed three approaches: (1) microarray expression analysis of genes previously implicated in fin regeneration, (2) RT-PCR analysis of genes newly identified as differentially expressed during regeneration, and (3)in situ hybridizationof the up-regulated genes bambi,dlx5A, and her6. Moreover, we show that Smad 1/5/8 proteins, effector molecules of Bmp signaling, are phosphorylated during fin regeneration. Taken together, we provide a comprehensive database of fin regeneration that will serve as an important tool for understanding the molecular mechanisms of regeneration.
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Böckelmann, PK, und IJ Bechara. „The regeneration of the tail fin actinotrichia of carp (Cyprinus carpio, Linnaeus, 1758) under the action of naproxen“. Brazilian Journal of Biology 69, Nr. 4 (November 2009): 1165–72. http://dx.doi.org/10.1590/s1519-69842009000500022.
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A conglomerate of small, rigid, fusiform spicules known as actinotrichia sustains the edge of tail fins of teleost. After amputation, these structures show an extremely fast regenerative capacity. In this study we observed the effect of a nonsteroidal anti-inflammatory drug, naproxen, used in the treatment of degenerative articular diseases, during the process of actinotrichia regeneration. For this purpose, regenerating tissue from animals in contact with the drug was submitted to histochemical and ultrastructural analysis in comparison to tissue from animals under normal conditions, i.e., not in contact with the drug in question. Actinotrichia regeneration was similar in both animals, indicating that naproxen, at the dose used in the present study, did not interfere with actinotrichia synthesis during the regenerative process of the tail fin. This could be because naproxen did not influence the expression of the genes required for the regeneration process, such as the Sonic hedgehog (Shh) gene, which is involved in actinotrichia formation.
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Dolan, Connor P., Lindsay A. Dawson und Ken Muneoka. „Digit Tip Regeneration: Merging Regeneration Biology with Regenerative Medicine“. STEM CELLS Translational Medicine 7, Nr. 3 (05.02.2018): 262–70. http://dx.doi.org/10.1002/sctm.17-0236.
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Cahaya, Cindy, und Sri Lelyati C. Masulili. „Perkembangan Terkini Membran Guided Tissue Regeneration/Guided Bone Regeneration sebagai Terapi Regenerasi Jaringan Periodontal“. Majalah Kedokteran Gigi Indonesia 1, Nr. 1 (01.06.2015): 1. http://dx.doi.org/10.22146/majkedgiind.8810.
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Periodontitis adalah salah satu penyakit patologis yang mempengaruhi integritas sistem periodontal yang menyebabkan kerusakan jaringan periodontal yang berlanjut pada kehilangan gigi. Beberapa tahun belakangan ini banyak ketertarikan untuk melakukan usaha regenerasi jaringan periodontal, tidak saja untuk menghentikan proses perjalanan penyakit namun juga mengembalikan jaringan periodontal yang telah hilang. Sasaran dari terapi regeneratif periodontal adalah menggantikan tulang, sementum dan ligamentum periodontal pada permukaan gigi yang terkena penyakit. Prosedur regenerasi antara lain berupa soft tissue graft, bone graft, biomodifikasi akar gigi, guided tissue regeneration sertakombinasi prosedur-prosedur di atas, termasuk prosedur bedah restoratif yang berhubungan dengan rehabilitasi oral dengan penempatan dental implan. Pada tingkat selular, regenerasi periodontal adalah proses kompleks yang membutuhkan proliferasi yang terorganisasi, differensiasi dan pengembangan berbagai tipe sel untuk membentuk perlekatan periodontal. Rasionalisasi penggunaan guided tissue regeneration sebagai membran pembatas adalah menahan epitel dan gingiva jaringan pendukung, sebagai barrier membrane mempertahankan ruang dan gigi serta menstabilkan bekuan darah. Pada makalah ini akan dibahas sekilas mengenai 1. Proses penyembuhan terapi periodontal meliputi regenerasi, repair ataupun pembentukan perlekatan baru. 2. Periodontal spesific tissue engineering. 3. Berbagai jenis membran/guided tissue regeneration yang beredar di pasaran dengan keuntungan dan kerugian sekaligus karakteristik masing-masing membran. 4. Perkembangan membran terbaru sebagai terapi regenerasi penyakit periodontal. Tujuan penulisan untuk memberi gambaran masa depan mengenai terapi regenerasi yang menjanjikan sebagai perkembangan terapi penyakit periodontal. Latest Development of Guided Tissue Regeneration and Guided Bone Regeneration Membrane as Regenerative Therapy on Periodontal Tissue. Periodontitis is a patological state which influences the integrity of periodontal system that could lead to the destruction of the periodontal tissue and end up with tooth loss. Currently, there are so many researches and efforts to regenerate periodontal tissue, not only to stop the process of the disease but also to reconstruct the periodontal tissue. Periodontal regenerative therapy aims at directing the growth of new bone, cementum and periodontal ligament on the affected teeth. Regenerative procedures consist of soft tissue graft, bone graft, roots biomodification, guided tissue regeneration and combination of the procedures, including restorative surgical procedure that is connected with oral rehabilitation with implant placement. At cellular phase, periodontal regeneration is a complex process with well-organized proliferation, distinction, and development of various type of cell to form attachment of periodontal tissue. Rationalization of the use of guided tissue regeneration as barrier membrane is to prohibit the penetration of epithelial and connective tissue migration into the defect, to maintain space, and to stabilize the clot. This research discusses: 1. Healing process on periodontal therapy including regeneration, repair or formation of new attachment. 2. Periodontal specific tissue engineering. 3. Various commercially available membrane/guided tissue regeneration in the market with its advantages and disadvantages and their characteristics. 4. Recent advancement of membrane as regenerative therapy on periodontal disease. In addition, this review is presented to give an outlook for promising regenerative therapy as a part of developing knowledge and skills to treat periodontal disease.
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Springhetti, Sina, Vesna Bucan, Christina Liebsch, Andrea Lazaridis, Peter Maria Vogt und Sarah Strauß. „An Identification and Characterization of the Axolotl (Ambystoma mexicanum, Amex) Telomerase Reverse Transcriptase (Amex TERT)“. Genes 13, Nr. 2 (18.02.2022): 373. http://dx.doi.org/10.3390/genes13020373.
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The Mexican axolotl is one of the few vertebrates that is able to replace its lost body parts during lifespan. Due to its remarkable regenerative abilities, the axolotl emerged as a model organism especially for limb regeneration. Telomeres and the telomerase enzyme are crucial for regeneration and protection against aging processes and degenerating diseases. Despite its relevance for regeneration, the axolotl telomerase and telomere length have not yet been investigated. Therefore, in the present paper, we reveal the sequence of the axolotl telomerase reverse transcriptase gene (Tert) and protein (TERT). Multiple sequence alignment (MSA) showed the known conserved RT- and TERT-specific motifs and residues found in other TERTs. In addition, we establish methods to determine the Tert expression (RT-PCR) and telomerase activity (Q-TRAP) of adult axolotl and blastema tissues. We found that both differentiated forelimb tissue and regenerating blastema tissue express Tert and show telomerase activity. Furthermore, blastema tissue appears to exhibit a higher Tert expression and telomerase activity. The presence of active telomerase in adult somatic cells is a decisive difference to somatic cells of non-regenerating vertebrates, such as humans. These findings indicate that telomere biology may play a key role in the regenerative abilities of cells.
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Milyavsky, Maresha, und Renee Dickie. „Methylene Blue Assay for Estimation of Regenerative Re-Epithelialization In Vivo“. Microscopy and Microanalysis 23, Nr. 1 (Februar 2017): 113–21. http://dx.doi.org/10.1017/s1431927617000101.
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AbstractThe rapidity with which epithelial cells cover a wound surface helps determine whether scarring or scar-less healing results. As methylene blue is a vital dye that is absorbed by damaged tissue but not undamaged epidermis, it can be used to assess wound closure. We sought to develop a quantitative methylene blue exclusion assay to estimate the timeframe for re-epithelialization in regenerating appendages in zebrafish and axolotls, two classic model systems of regeneration. Following application of methylene blue to the amputation plane and extensive washing, the regenerating tail was imaged in vivo until staining was no longer visible. The percent area of the amputation plane positive for methylene blue, representing the area of the amputation plane not yet re-epithelialized, was measured for each time point. The loss of methylene blue occurred rapidly, within ~2.5 h in larval and juvenile axolotls and <1 h in adult zebrafish, consistent with high rates of re-epithelialization in these models of regeneration. The assay allows simple, rapid estimation of the time course for regenerative re-epithelialization without affecting subsequent regenerative ability. This technique will permit comparison of re-epithelialization across different strains and stages, as well as under the influence of various pharmacological inhibitors that affect regeneration.
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Di-Iacovo, Nicola, Stefania Pieroni, Danilo Piobbico, Marilena Castelli, Damiano Scopetti, Simona Ferracchiato, Maria Agnese Della-Fazia und Giuseppe Servillo. „Liver Regeneration and Immunity: A Tale to Tell“. International Journal of Molecular Sciences 24, Nr. 2 (07.01.2023): 1176. http://dx.doi.org/10.3390/ijms24021176.
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The physiological importance of the liver is demonstrated by its unique and essential ability to regenerate following extensive injuries affecting its function. By regenerating, the liver reacts to hepatic damage and thus enables homeostasis to be restored. The aim of this review is to add new findings that integrate the regenerative pathway to the current knowledge. An optimal regeneration is achieved through the integration of two main pathways: IL-6/JAK/STAT3, which promotes hepatocyte proliferation, and PI3K/PDK1/Akt, which in turn enhances cell growth. Proliferation and cell growth are events that must be balanced during the three phases of the regenerative process: initiation, proliferation and termination. Achieving the correct liver/body weight ratio is ensured by several pathways as extracellular matrix signalling, apoptosis through caspase-3 activation, and molecules including transforming growth factor-beta, and cyclic adenosine monophosphate. The actors involved in the regenerative process are numerous and many of them are also pivotal players in both the immune and non-immune inflammatory process, that is observed in the early stages of hepatic regeneration. Balance of Th17/Treg is important in liver inflammatory process outcomes. Knowledge of liver regeneration will allow a more detailed characterisation of the molecular mechanisms that are crucial in the interplay between proliferation and inflammation.
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Alhajlah, Sharif, Adam M. Thompson und Zubair Ahmed. „Overexpression of Reticulon 3 Enhances CNS Axon Regeneration and Functional Recovery after Traumatic Injury“. Cells 10, Nr. 8 (06.08.2021): 2015. http://dx.doi.org/10.3390/cells10082015.
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CNS neurons are generally incapable of regenerating their axons after injury due to several intrinsic and extrinsic factors, including the presence of axon growth inhibitory molecules. One such potent inhibitor of CNS axon regeneration is Reticulon (RTN) 4 or Nogo-A. Here, we focused on RTN3 as its contribution to CNS axon regeneration is currently unknown. We found that RTN3 expression correlated with an axon regenerative phenotype in dorsal root ganglion neurons (DRGN) after injury to the dorsal columns, a well-characterised model of spinal cord injury. Overexpression of RTN3 promoted disinhibited DRGN neurite outgrowth in vitro and dorsal column axon regeneration/sprouting and electrophysiological, sensory and locomotor functional recovery after injury in vivo. Knockdown of protrudin, however, ablated RTN3-enhanced neurite outgrowth/axon regeneration in vitro and in vivo. Moreover, overexpression of RTN3 in a second model of CNS injury, the optic nerve crush injury model, enhanced retinal ganglion cell (RGC) survival, disinhibited neurite outgrowth in vitro and survival and axon regeneration in vivo, an effect that was also dependent on protrudin. These results demonstrate that RTN3 enhances neurite outgrowth/axon regeneration in a protrudin-dependent manner after both spinal cord and optic nerve injury.
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Rotter, Nicole, und Marcy Zenobi-Wong. „Regeneration – eine neue therapeutische Dimension in der Hals-Nasen-Ohrenheilkunde“. Laryngo-Rhino-Otologie 97, S 01 (März 2018): S185—S213. http://dx.doi.org/10.1055/s-0043-122309.
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ZusammenfassungDie Regeneration als therapeutisches Prinzip und damit die Regenerative Medizin ist ein vielversprechender Ansatz künftig die therapeutischen Optionen der Hals-Nasen-Ohrenheilkunde um eine weitere Dimension zu erweitern. Während heute rekonstruktive chirurgische Verfahren, Medikamente und Prothesen wie bspw. das Cochlea Implantat die Funktionen defekter Gewebe im Kopf-Hals-Bereich ersetzen, sollen durch die Regenerative Medizin die defekten Gewebe und deren Funktion selbst wiederhergestellt werden. In dieser Übersichtsarbeit werden neue Entwicklungen wie das 3D-Bioprinting und dezellularisierte, natürliche Biomaterialien für regenerative Ansätze vorgestellt und durch eine Zusammenstellung aktueller präklinischer und klinischer Studien im Bereich der Regenerativen Medizin in der Hals-Nasen-Ohrenheilkunde ergänzt.
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Saberian, Elham, Andrej Jenča, Yaser Zafari, Andrej Jenča, Adriána Petrášová, Hadi Zare-Zardini und Janka Jenčová. „Scaffold Application for Bone Regeneration with Stem Cells in Dentistry: Literature Review“. Cells 13, Nr. 12 (19.06.2024): 1065. http://dx.doi.org/10.3390/cells13121065.
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Bone tissue injuries within oral and dental contexts often present considerable challenges because traditional treatments may not be able to fully restore lost or damaged bone tissue. Novel approaches involving stem cells and targeted 3D scaffolds have been investigated in the search for workable solutions. The use of scaffolds in stem cell-assisted bone regeneration is a crucial component of tissue engineering techniques designed to overcome the drawbacks of traditional bone grafts. This study provides a detailed review of scaffold applications for bone regeneration with stem cells in dentistry. This review focuses on scaffolds and stem cells while covering a broad range of studies explaining bone regeneration in dentistry through the presentation of studies conducted in this field. The role of different stem cells in regenerative medicine is covered in great detail in the reviewed literature. These studies have addressed a wide range of subjects, including the effects of platelet concentrates during dental surgery or specific combinations, such as human dental pulp stem cells with scaffolds for animal model bone regeneration, to promote bone regeneration in animal models. Noting developments, research works consider methods to improve vascularization and explore the use of 3D-printed scaffolds, secretome applications, mesenchymal stem cells, and biomaterials for oral bone tissue regeneration. This thorough assessment outlines possible developments within these crucial regenerative dentistry cycles and provides insights and suggestions for additional study. Furthermore, alternative creative methods for regenerating bone tissue include biophysical stimuli, mechanical stimulation, magnetic field therapy, laser therapy, nutritional supplements and diet, gene therapy, and biomimetic materials. These innovative approaches offer promising avenues for future research and development in the field of bone tissue regeneration in dentistry.
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Sandra, Ferry, Andri Sutanto, Widya Wulandari, Reynaldo Lambertus, Maria Celinna, Nurrani Mustika Dewi und Solachuddin Jauhari Arief Ichwan. „Crucial Triad in Pulp-Dentin Complex Regeneration: Dental Stem Cells, Scaffolds, and Signaling Molecules“. Indonesian Biomedical Journal 15, Nr. 1 (23.02.2023): 25–46. http://dx.doi.org/10.18585/inabj.v15i1.2265.
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BACKGROUND: Pulp damage can lead to dentinogenesis impairment, irreversible pulpitis, or pulp necrosis. Despite being the most used endodontic procedure to treat damaged pulp, root canal therapy only results in nonvital teeth which are prone to fractures and secondary infection. Pulp-dentin regeneration has a potential to regenerate structure similar to normal pulp-dentin complex, and can be achieved by combining dental stem cells, scaffold, and signaling molecules. This article reviews the role of various types of dental stem cells, scaffolds, signaling molecules, and their combinations in regenerating pulp-dentin complex.CONTENT: Dental pulp stem cell (DPSC), stem cell from human exfoliated deciduous teeth (SHED), and dental follicle stem cell (DFSC) were reported to regenerate pulp-dentin complex in situ. SHED might be more promising than DPSCs and DFSCs for regenerating pulp-dentin complex, since SHED have a higher proliferation potential and higher expression levels of signaling molecules. Scaffolds have characteristics resembling extracellular matrix, thus providing a suitable microenvironment for transplanted dental stem cells. To accelerate the regeneration process, exogenous signaling molecules are often delivered together with dental stem cells. Scaffolds and signaling molecules have different regenerative potential, including induction of cell proliferation and migration, formation of pulp- and/or dentin-like tissue, as well as angiogenesis and neurogenesis promotion.SUMMARY: Combinations of dental stem cells, scaffold, and signaling molecules are important to achieve the functional pulp-dentin complex formation. Current trends and future directions on regenerative endodontics should be explored. The right combination of dental stem cells, scaffold, and signaling molecules could be determined based on the patients’ characteristics. Incomplete pulp-dentin regeneration could be overcome by applying dental stem cells, scaffold, and/or signaling molecules in multiple visits.KEYWORDS: pulp-dentin regeneration, regenerative endodontics, dental stem cells, scaffold, signaling molecules
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Ikeda, Etsuko, Miho Ogawa, Makoto Takeo und Takashi Tsuji. „Functional ectodermal organ regeneration as the next generation of organ replacement therapy“. Open Biology 9, Nr. 3 (März 2019): 190010. http://dx.doi.org/10.1098/rsob.190010.
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In this decade, substantial progress in the fields of developmental biology and stem cell biology has ushered in a new era for three-dimensional organ regenerative therapy. The emergence of novel three-dimensional cell manipulation technologies enables the effective mimicking of embryonic organ germ formation using the fate-determined organ-inductive potential of epithelial and mesenchymal stem cells. This advance shows great potential for the regeneration of functional organs with substitution of complete original function in situ . Organoids generated from multipotent stem cells or tissue stem cells via establishment of an organ-forming field can only partially recover original organ function owing to the size limitation; they are considered ‘mini-organs’. Nevertheless, they hold great promise to realize regenerative medicine. In particular, regeneration of a functional salivary gland and an integumentary organ system by orthotopic and heterotopic implantation of organoids clearly points to the future direction of organ regeneration research. In this review, we describe multiple strategies and recent progress in regenerating functional three-dimensional organs, focusing on ectodermal organs, and discuss their potential and future directions to achieve organ replacement therapy as a next-generation regenerative medicine.
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Marshall, Lindsey N., Céline J. Vivien, Fabrice Girardot, Louise Péricard, Pierluigi Scerbo, Karima Palmier, Barbara A. Demeneix und Laurent Coen. „Stage-dependent cardiac regeneration in Xenopus is regulated by thyroid hormone availability“. Proceedings of the National Academy of Sciences 116, Nr. 9 (12.02.2019): 3614–23. http://dx.doi.org/10.1073/pnas.1803794116.
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Despite therapeutic advances, heart failure is the major cause of morbidity and mortality worldwide, but why cardiac regenerative capacity is lost in adult humans remains an enigma. Cardiac regenerative capacity widely varies across vertebrates. Zebrafish and newt hearts regenerate throughout life. In mice, this ability is lost in the first postnatal week, a period physiologically similar to thyroid hormone (TH)-regulated metamorphosis in anuran amphibians. We thus assessed heart regeneration in Xenopus laevis before, during, and after TH-dependent metamorphosis. We found that tadpoles display efficient cardiac regeneration, but this capacity is abrogated during the metamorphic larval-to-adult switch. Therefore, we examined the consequence of TH excess and deprivation on the efficiently regenerating tadpole heart. We found that either acute TH treatment or blocking TH production before resection significantly but differentially altered gene expression and kinetics of extracellular matrix components deposition, and negatively impacted myocardial wall closure, both resulting in an impeded regenerative process. However, neither treatment significantly influenced DNA synthesis or mitosis in cardiac tissue after amputation. Overall, our data highlight an unexplored role of TH availability in modulating the cardiac regenerative outcome, and present X. laevis as an alternative model to decipher the developmental switches underlying stage-dependent constraint on cardiac regeneration.
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Lu, Fangfang, Lyndsay L. Leach und Jeffrey M. Gross. „mTOR activity is essential for retinal pigment epithelium regeneration in zebrafish“. PLOS Genetics 18, Nr. 3 (10.03.2022): e1009628. http://dx.doi.org/10.1371/journal.pgen.1009628.
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The retinal pigment epithelium (RPE) plays numerous critical roles in maintaining vision and this is underscored by the prevalence of degenerative blinding diseases like age-related macular degeneration (AMD), in which visual impairment is caused by progressive loss of RPE cells. In contrast to mammals, zebrafish possess the ability to intrinsically regenerate a functional RPE layer after severe injury. The molecular underpinnings of this regenerative process remain largely unknown yet hold tremendous potential for developing treatment strategies to stimulate endogenous regeneration in the human eye. In this study, we demonstrate that the mTOR pathway is activated in RPE cells post-genetic ablation. Pharmacological and genetic inhibition of mTOR activity impaired RPE regeneration, while mTOR activation enhanced RPE recovery post-injury, demonstrating that mTOR activity is essential for RPE regeneration in zebrafish. RNA-seq of RPE isolated from mTOR-inhibited larvae identified a number of genes and pathways dependent on mTOR activity at early and late stages of regeneration; amongst these were components of the immune system, which is emerging as a key regulator of regenerative responses across various tissue and model systems. Our results identify crosstalk between macrophages/microglia and the RPE, wherein mTOR activity is required for recruitment of macrophages/microglia to the RPE injury site. Macrophages/microglia then reinforce mTOR activity in regenerating RPE cells. Interestingly, the function of macrophages/microglia in maintaining mTOR activity in the RPE appeared to be inflammation-independent. Taken together, these data identify mTOR activity as a key regulator of RPE regeneration and link the mTOR pathway to immune responses in facilitating RPE regeneration.
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Yang, Lin, Jinge Sun, Congyu Yan, Junyi Wu, Yaya Wang, Qiuting Ren, Shen Wang, Xu Ma, Ling Zhao und Jinsheng Sun. „Regeneration of duckweed (Lemna turonifera) involves genetic molecular regulation and cyclohexane release“. PLOS ONE 17, Nr. 1 (06.01.2022): e0254265. http://dx.doi.org/10.1371/journal.pone.0254265.
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Plant regeneration is important for vegetative propagation, detoxification and the obtain of transgenic plant. We found that duckweed regeneration could be enhanced by regenerating callus. However, very little is known about the molecular mechanism and the release of volatile organic compounds (VOCs). To gain a global view of genes differently expression profiles in callus and regenerating callus, genetic transcript regulation has been studied. Auxin related genes have been significantly down-regulated in regenerating callus. Cytokinin signal pathway genes have been up-regulated in regenerating callus. This result suggests the modify of auxin and cytokinin balance determines the regenerating callus. Volatile organic compounds release has been analysised by gas chromatography/ mass spectrum during the stage of plant regeneration, and 11 kinds of unique volatile organic compounds in the regenerating callus were increased. Cyclohexane treatment enhanced duckweed regeneration by initiating root. Moreover, Auxin signal pathway genes were down-regulated in callus treated by cyclohexane. All together, these results indicated that cyclohexane released by regenerating callus promoted duckweed regeneration. Our results provide novel mechanistic insights into how regenerating callus promotes regeneration.
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Murakami, Mineko, Chizuka Ide und Haruyuki Kanaya. „Regeneration in the rat optic nerve after cold injury“. Journal of Neurosurgery 71, Nr. 2 (August 1989): 254–65. http://dx.doi.org/10.3171/jns.1989.71.2.0254.
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✓ In order to examine nerve regeneration under conditions in which the basal laminae of the glial limiting membranes (GLM) and blood vessels were preserved intact, the intraorbital segment of adult rat optic nerve was frozen locally. During the next 3 months, degenerative and regenerative changes in axons and glial cells were observed by light and electron microscopy. On the day after treatment, all the myelinated and unmyelinated axons in the central zone of the lesion were damaged. The astrocyte endfeet of the GLM as well as the blood vessels were extensively disrupted, while their basal laminae were preserved apparently intact as a continuous sheet. Three days after treatment, regenerating axons appeared in the central zone of the lesion. They contained various numbers of clear and dense-cored vesicles as well as some smooth endoplasmic reticulum. The regenerating axons gradually increased in number, especially beneath the pial and perivascular surfaces of the lesion, where an abundance of regenerating axons was found 3 months after treatment. A few of these axons were abnormally remyelinated by oligodendrocytes. In addition to this axonal regeneration through the intraoptic nerve compartment, fine regenerating axons were seen growing out through GLM into the pial connective tissue 3 weeks after treatment. Astrocyte endfeet of the GLM became irregular in contour, protruding in a fern-leaf fashion into the pial connective tissue. Fine naked axons grew out through these protrusions and subsequently increased in number, vigorously growing in large bundles both proximally and distally along blood vessels in the pial connective tissue. Bundles of regenerating axons extended as much as 1.5 mm from the site of the lesion 3 months after surgery. These bundles were covered by thin processes of pial or arachnoidal non-neuronal cells, and the regenerating axons remained unmyelinated. The above findings indicate that under well-nourished conditions, adult mammalian optic nerve exhibits considerable regenerative ability.
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Funda, Goker, Silvio Taschieri, Giannì Aldo Bruno, Emma Grecchi, Savadori Paolo, Donati Girolamo und Massimo Del Fabbro. „Nanotechnology Scaffolds for Alveolar Bone Regeneration“. Materials 13, Nr. 1 (03.01.2020): 201. http://dx.doi.org/10.3390/ma13010201.
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In oral biology, tissue engineering aims at regenerating functional tissues through a series of key events that occur during alveolar/periodontal tissue formation and growth, by means of scaffolds that deliver signaling molecules and cells. Due to their excellent physicochemical properties and biomimetic features, nanomaterials are attractive alternatives offering many advantages for stimulating cell growth and promoting tissue regeneration through tissue engineering. The main aim of this article was to review the currently available literature to provide an overview of the different nano-scale scaffolds as key factors of tissue engineering for alveolar bone regeneration procedures. In this narrative review, PubMed, Medline, Scopus and Cochrane electronic databases were searched using key words like “tissue engineering”, “regenerative medicine”, “alveolar bone defects”, “alveolar bone regeneration”, “nanomaterials”, “scaffolds”, “nanospheres” and “nanofibrous scaffolds”. No limitation regarding language, publication date and study design was set. Hand-searching of the reference list of identified articles was also undertaken. The aim of this article was to give a brief introduction to review the role of different nanoscaffolds for bone regeneration and the main focus was set to underline their role for alveolar bone regeneration procedures.