Relevant bibliographies by topics / Mesenchymal stem cells, reprogramming, differentiation

Academic literature on the topic 'Mesenchymal stem cells, reprogramming, differentiation'

Author: Grafiati
Published: 9 March 2023
Last updated: 10 March 2023

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Journal articles on the topic "Mesenchymal stem cells, reprogramming, differentiation"

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Abdal Dayem, Ahmed, Soo Bin Lee, Kyeongseok Kim, Kyung Min Lim, Tak-il Jeon, Jaekwon Seok, and Ssang-Goo Cho. "Production of Mesenchymal Stem Cells Through Stem Cell Reprogramming." International Journal of Molecular Sciences 20, no. 8 (April 18, 2019): 1922. http://dx.doi.org/10.3390/ijms20081922.

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Mesenchymal stem cells (MSCs) possess a broad spectrum of therapeutic applications and have been used in clinical trials. MSCs are mainly retrieved from adult or fetal tissues. However, there are many obstacles with the use of tissue-derived MSCs, such as shortages of tissue sources, difficult and invasive retrieval methods, cell population heterogeneity, low purity, cell senescence, and loss of pluripotency and proliferative capacities over continuous passages. Therefore, other methods to obtain high-quality MSCs need to be developed to overcome the limitations of tissue-derived MSCs. Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are considered potent sources for the derivation of MSCs. PSC-derived MSCs (PSC-MSCs) may surpass tissue-derived MSCs in proliferation capacity, immunomodulatory activity, and in vivo therapeutic applications. In this review, we will discuss basic as well as recent protocols for the production of PSC-MSCs and their in vitro and in vivo therapeutic efficacies. A better understanding of the current advances in the production of PSC-MSCs will inspire scientists to devise more efficient differentiation methods that will be a breakthrough in the clinical application of PSC-MSCs.
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Hsu, Yi-Chao, Yu-Ting Wu, Chia-Ling Tsai, and Yau-Huei Wei. "Current understanding and future perspectives of the roles of sirtuins in the reprogramming and differentiation of pluripotent stem cells." Experimental Biology and Medicine 243, no. 6 (March 2018): 563–75. http://dx.doi.org/10.1177/1535370218759636.

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In mammalian cells, there are seven members of the sirtuin protein family (SIRT1–7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a–SIRT1–p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells. SIRT4 has no direct role in regulating reprogramming but may have the potential to prevent senescence of somatic cells and to facilitate the reprogramming of iPSCs. SIRT5 can deacetylate STAT3, which is an important transcription factor in regulating pluripotency and differentiation of stem cells. SIRT6 can enhance the reprogramming efficiency of iPSCs from aged skin fibroblasts through miR-766 and increase the expression levels of the reprogramming genes including Sox2, Oct4, and Nanog through acetylation of histone H3 lysine 56. SIRT7 plays a regulatory role in the process of mesenchymal-to-epithelial transition (MET), which has been suggested to be a crucial process in the generation of iPSCs from fibroblasts. In this review, we summarize recent findings of the roles of sirtuins in the metabolic reprogramming and differentiation of stem cells and discuss the bidirectional changes in the gene expression and activities of sirtuins in the commitment of differentiation of mesenchymal stem cells (MSCs) and reprogramming of somatic cells to iPSCs, respectively. Thus, understanding the molecular basis of the interplay between different sirtuins and mitochondrial function will provide new insights into the regulation of differentiation of stem cells and iPSCs formation, respectively, and may help design effective stem cell therapies for regenerative medicine. Impact statement This is an extensive review of the recent advances in our understanding of the roles of some members of the sirtuins family, such as SIRT1, SIRT2, SIRT3, and SIRT6, in the regulation of intermediary metabolism during stem cell differentiation and in the reprogramming of somatic cells to form induced pluripotent stem cells (iPSCs). This article provides an updated integrated view on the mechanisms by which sirtuins-mediated posttranslational protein modifications regulate mitochondrial biogenesis, bioenergetics, and antioxidant defense in the maintenance and differentiation of stem cells and in iPSCs formation, respectively.
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Umrath, Felix, Marbod Weber, Siegmar Reinert, Hans-Peter Wendel, Meltem Avci-Adali, and Dorothea Alexander. "iPSC-Derived MSCs Versus Originating Jaw Periosteal Cells: Comparison of Resulting Phenotype and Stem Cell Potential." International Journal of Molecular Sciences 21, no. 2 (January 16, 2020): 587. http://dx.doi.org/10.3390/ijms21020587.

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Induced pluripotent stem cell-derived mesenchymal stem cell-like cells (iMSCs) are considered to be a promising source of progenitor cells for approaches in the field of bone regeneration. In a previous study, we described the generation of footprint-free induced pluripotent stem cells (iPSCs) from human jaw periosteal cells (JPCs) by transfection of a self-replicating RNA (srRNA) and subsequent differentiation into functional osteogenic progenitor cells. In order to facilitate the prospective transfer into clinical practice, xeno-free reprogramming and differentiation methods were established. In this study, we compared the properties and stem cell potential of the iMSCs produced from JPC-derived iPSCs with the parental primary JPCs they were generated from. Our results demonstrated, on the one hand, a comparable differentiation potential of iMSCs and JPCs. Additionally, iMSCs showed significantly longer telomere lengths compared to JPCs indicating rejuvenation of the cells during reprogramming. On the other hand, proliferation, mitochondrial activity, and senescence-associated beta-galactosidase (SA-β-gal) activity indicated early senescence of iMSCs. These data demonstrate the requirement of further optimization strategies to improve mesenchymal development of JPC-derived iPSCs in order to take advantage of the best features of reprogrammed and rejuvenated cells.
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Wang, Aline Yen Ling. "Application of Modified mRNA in Somatic Reprogramming to Pluripotency and Directed Conversion of Cell Fate." International Journal of Molecular Sciences 22, no. 15 (July 29, 2021): 8148. http://dx.doi.org/10.3390/ijms22158148.

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Modified mRNA (modRNA)-based somatic reprogramming is an effective and safe approach that overcomes the genomic mutation risk caused by viral integrative methods. It has improved the disadvantages of conventional mRNA and has better stability and immunogenicity. The modRNA molecules encoding multiple pluripotent factors have been applied successfully in reprogramming somatic cells such as fibroblasts, mesenchymal stem cells, and amniotic fluid stem cells to generate pluripotent stem cells (iPSCs). Moreover, it also can be directly used in the terminal differentiation of stem cells and fibroblasts into functional therapeutic cells, which exhibit great promise in disease modeling, drug screening, cell transplantation therapy, and regenerative medicine. In this review, we summarized the reprogramming applications of modified mRNA in iPSC generation and therapeutic applications of functionally differentiated cells.
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Ramazzotti, Ratti, Fiume, Yung Follo, Billi, Rusciano, Owusu Obeng, Manzoli, Cocco, and Faenza. "Phosphoinositide 3 Kinase Signaling in Human Stem Cells from Reprogramming to Differentiation: A Tale in Cytoplasmic and Nuclear Compartments." International Journal of Molecular Sciences 20, no. 8 (April 24, 2019): 2026. http://dx.doi.org/10.3390/ijms20082026.

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Stem cells are undifferentiated cells that can give rise to several different cell types and can self-renew. Given their ability to differentiate into different lineages, stem cells retain huge therapeutic potential for regenerative medicine. Therefore, the understanding of the signaling pathways involved in stem cell pluripotency maintenance and differentiation has a paramount importance in order to understand these biological processes and to develop therapeutic strategies. In this review, we focus on phosphoinositide 3 kinase (PI3K) since its signaling pathway regulates many cellular processes, such as cell growth, proliferation, survival, and cellular transformation. Precisely, in human stem cells, the PI3K cascade is involved in different processes from pluripotency and induced pluripotent stem cell (iPSC) reprogramming to mesenchymal and oral mesenchymal differentiation, through different and interconnected mechanisms.
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Eguchi, Takanori, and Takuo Kuboki. "Cellular Reprogramming Using Defined Factors and MicroRNAs." Stem Cells International 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/7530942.

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Development of human bodies, organs, and tissues contains numerous steps of cellular differentiation including an initial zygote, embryonic stem (ES) cells, three germ layers, and multiple expertized lineages of cells. Induced pluripotent stem (iPS) cells have been recently developed using defined reprogramming factors such as Nanog, Klf5, Oct3/4 (Pou5f1), Sox2, and Myc. This outstanding innovation is largely changing life science and medicine. Methods of direct reprogramming of cells into myocytes, neurons, chondrocytes, and osteoblasts have been further developed using modified combination of factors such as N-myc, L-myc, Sox9, and microRNAs in defined cell/tissue culture conditions. Mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) are also emerging multipotent stem cells with particular microRNA expression signatures. It was shown that miRNA-720 had a role in cellular reprogramming through targeting the pluripotency factor Nanog and induction of DNA methyltransferases (DNMTs). This review reports histories, topics, and idea of cellular reprogramming.
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Moslem, Mohsen, Irina Eberle, Iuliia Weber, Reinhard Henschler, and Tobias Cantz. "Mesenchymal Stem/Stromal Cells Derived from Induced Pluripotent Stem Cells Support CD34posHematopoietic Stem Cell Propagation and Suppress Inflammatory Reaction." Stem Cells International 2015 (2015): 1–14. http://dx.doi.org/10.1155/2015/843058.

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Mesenchymal stem/stromal cells (MSCs) represent a promising cell source for research and therapeutic applications, but their restrictedex vivopropagation capabilities limit putative applications. Substantial self-renewing of stem cells can be achieved by reprogramming cells into induced pluripotent stem cells (iPSCs) that can be easily expanded as undifferentiated cells even in mass culture. Here, we investigated a differentiation protocol enabling the generation and selection of human iPSC-derived MSCs exhibiting relevant surface marker expression profiles (CD105 and CD73) and functional characteristics. We generated such iPSC-MSCs from fibroblasts and bone marrow MSCs utilizing two different reprogramming constructs. All such iPSC-MSCs exhibited the characteristics of normal bone marrow-derived (BM) MSCs. In direct comparison to BM-MSCs our iPSC-MSCs exhibited a similar surface marker expression profile but shorter doubling times without reaching senescence within 20 passages. Considering functional capabilities, iPSC-MSCs provided supportive feeder layer for CD34+hematopoietic stem cells’ self-renewal and colony forming capacities. Furthermore, iPSC-MSCs gained immunomodulatory function to suppress CD4+cell proliferation, reduce proinflammatory cytokines in mixed lymphocyte reaction, and increase regulatory CD4+/CD69+/CD25+T-lymphocyte population. In conclusion, we generated fully functional MSCs from various iPSC lines irrespective of their starting cell source or reprogramming factor composition and we suggest that such iPSC-MSCs allow repetitive cell applications for advanced therapeutic approaches.
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Mueller, Paula, Markus Wolfien, Katharina Ekat, Cajetan Immanuel Lang, Dirk Koczan, Olaf Wolkenhauer, Olga Hahn, et al. "RNA-Based Strategies for Cardiac Reprogramming of Human Mesenchymal Stromal Cells." Cells 9, no. 2 (February 22, 2020): 504. http://dx.doi.org/10.3390/cells9020504.

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Multipotent adult mesenchymal stromal cells (MSCs) could represent an elegant source for the generation of patient-specific cardiomyocytes needed for regenerative medicine, cardiovascular research, and pharmacological studies. However, the differentiation of adult MSC into a cardiac lineage is challenging compared to embryonic stem cells or induced pluripotent stem cells. Here we used non-integrative methods, including microRNA and mRNA, for cardiac reprogramming of adult MSC derived from bone marrow, dental follicle, and adipose tissue. We found that MSC derived from adipose tissue can partly be reprogrammed into the cardiac lineage by transient overexpression of GATA4, TBX5, MEF2C, and MESP1, while cells isolated from bone marrow, and dental follicle exhibit only weak reprogramming efficiency. qRT-PCR and transcriptomic analysis revealed activation of a cardiac-specific gene program and up-regulation of genes known to promote cardiac development. Although we did not observe the formation of fully mature cardiomyocytes, our data suggests that adult MSC have the capability to acquire a cardiac-like phenotype when treated with mRNA coding for transcription factors that regulate heart development. Yet, further optimization of the reprogramming process is mandatory to increase the reprogramming efficiency.
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Tran, Van Hong, Hoa Trong Nguyen, and Phuc Van Pham. "Conversion of human adipose derived stem cells into endothelial progenitor cells." Progress in Stem Cell 4, no. 3-4 (November 29, 2017): 217–27. http://dx.doi.org/10.15419/psc.v4i3.396.

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Introduction: Endothelial cells (ECs) or endothelial progenitor cells (EPCs) are essential cells for blood vascular regeneration and vascular tissue engineering. However, the source of EPCs are limited. Indeed, these cells only existence with low rate at some tissues such as bone marrow, umbilical cord blood and peripheral blood. This study aimed to produce EPCs from direct reprogramming of adipose tissue-derived mesenchymal stem cells (ADSCs) by ETV2 transfection in vitro. Methods: ADSCs were isolated according to the published works. They were confirmed as mesenchymal stem cells (MSCs) with some characteristics included expression of CD44, CD73, CD90, negative of CD14, CD45, and HLA-DR; in vitro differentiation into adipocytes, and osteoblasts. ETV-2 mRNA was in vitro produced by commercial kit. ETV-2 mRNA molecules were transfected into ADSCs by Fugenes and Lipofectamine agents. These transfected cells were evaluated the expression of EPC properties included expression of CD31, VEGFR-2 in the cell surface by flow cytometry, immunocytochemistry, and in vitro vessel formation in the Matrigel. Results: The results showed that ETV-2 could transform the ADSCs from mesenchymal cell phenotype into endothelial cell phenotype with 10% transfected ADSCs expressing the CD31 in their surface, they also could form the vessel structure in vitro. Conclusion: Although the low efficacy of direct reprogramming, this study gave the new strategy to produce EPCs from the favorite cell sources as ADSCs.
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Teven, Chad M., Xing Liu, Ning Hu, Ni Tang, Stephanie H. Kim, Enyi Huang, Ke Yang, et al. "Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation." Stem Cells International 2011 (2011): 1–18. http://dx.doi.org/10.4061/2011/201371.

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Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Owing to their ease of isolation and unique characteristics, MSCs have been widely regarded as potential candidates for tissue engineering and repair. While various signaling molecules important to MSC differentiation have been identified, our complete understanding of this process is lacking. Recent investigations focused on the role of epigenetic regulation in lineage-specific differentiation of MSCs have shown that unique patterns of DNA methylation and histone modifications play an important role in the induction of MSC differentiation toward specific lineages. Nevertheless, MSC epigenetic profiles reflect a more restricted differentiation potential as compared to ES cells. Here we review the effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation. We also highlight clinical applications of MSC epigenetics and nuclear reprogramming.
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Dissertations / Theses on the topic "Mesenchymal stem cells, reprogramming, differentiation"

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Kaur, Navdeep. "Influence of culture conditions on the molecular signature of mesenchymal stem cells." Thesis, Queensland University of Technology, 2010. https://eprints.qut.edu.au/43719/1/Navdeep_Kaur_Thesis.pdf.

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Cell based therapies require cells capable of self renewal and differentiation, and a prerequisite is the ability to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies is therefore an integral part of tissue engineering. Bone marrow is the most easily accessible source of mesenchymal stem cells (MSCs), and harbours two distinct populations of adult stem cells; namely hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs). Unlike HSCs, there are yet no rigorous criteria for characterizing BMSCs. Changing understanding about the pluripotency of BMSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to BMSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their in vitro study. Also, when BMSCs are cultured in vitro there is a loss of the in vivo microenvironment which results in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage number, characterized by the onset of senescence related changes. Accordingly, establishing protocols for generating large numbers of BMSCs without affecting their differentiation potential is necessary. The principal aims of this thesis were to identify potential molecular factors for characterizing BMSCs from osteoarthritic patients, and also to attempt to establish culture protocols favourable for generating large number of BMSCs, while at the same time retaining their proliferation and differentiation potential. Previously published studies concerning clonal cells have demonstrated that BMSCs are heterogeneous populations of cells at various stages of growth. Some cells are higher in the hierarchy and represent the progenitors, while other cells occupy a lower position in the hierarchy and are therefore more committed to a particular lineage. This feature of BMSCs was made evident by the work of Mareddy et al., which involved generating clonal populations of BMSCs from bone marrow of osteoarthritic patients, by a single cell clonal culture method. Proliferation potential and differentiation capabilities were used to group cells into fast growing and slow growing clones. The study presented here is a continuation of the work of Mareddy et al. and employed immunological and array based techniques to identify the primary molecular factors involved in regulating phenotypic characteristics exhibited by contrasting clonal populations. The subtractive immunization (SI) was used to generate novel antibodies against favourably expressed proteins in the fast growing clonal cell population. The difference between the clonal populations at the transcriptional level was determined using a Stem Cell RT2 Profiler TM PCR Array which focuses on stem cell pathway gene expression. Monoclonal antibodies (mAb) generated by SI were able to effectively highlight differentially expressed antigenic determinants, as was evident by Western blot analysis and confocal microscopy. Co-immunoprecipitation, followed by mass spectroscopy analysis, identified a favourably expressed protein as the cytoskeletal protein vimentin. The stem cell gene array highlighted genes that were highly upregulated in the fast growing clonal cell population. Based on their functions these genes were grouped into growth factors, cell fate determination and maintenance of embryonic and neural stem cell renewal. Furthermore, on a closer analysis it was established that the cytoskeletal protein vimentin and nine out of ten genes identified by gene array were associated with chondrogenesis or cartilage repair, consistent with the potential role played by BMSCs in defect repair and maintaining tissue homeostasis, by modulating the gene expression pattern to compensate for degenerated cartilage in osteoarthritic tissues. The gene array also presented transcripts for embryonic lineage markers such as FOXA2 and Sox2, both of which were significantly over expressed in fast growing clonal populations. A recent groundbreaking study by Yamanaka et al imparted embryonic stem cell (ESCs) -like characteristic to somatic cells in a process termed nuclear reprogramming, by the ectopic expression of the genes Sox2, cMyc and Oct4. The expression of embryonic lineage markers in adult stem cells may be a mechanism by which the favourable behaviour of fast growing clonal cells is determined and suggests a possible active phenomenon of spontaneous reprogramming in fast growing clonal cells. The expression pattern of these critical molecular markers could be indicative of the competence of BMSCs. For this reason, the expression pattern of Sox2, Oct4 and cMyc, at various passages in heterogeneous BMSCs population and tissue derived cells (osteoblasts and chondrocytes), was investigated by a real-time PCR and immunoflourescence staining. A strong nuclear staining was observed for Sox2, Oct4 and cMyc, which gradually weakened accompanied with cytoplasmic translocation after several passage. The mRNA and protein expression of Sox2, Oct4 and cMyc peaked at the third passage for osteoblasts, chondrocytes and third passage for BMSCs, and declined with each subsequent passage, indicating towards a possible mechanism of spontaneous reprogramming. This study proposes that the progressive decline in proliferation potential and multipotentiality associated with increased passaging of BMSCs in vitro might be a consequence of loss of these propluripotency factors. We therefore hypothesise that the expression of these master genes is not an intrinsic cell function, but rather an outcome of interaction of the cells with their microenvironment; this was evident by the fact that when removed from their in vivo microenvironment, BMSCs undergo a rapid loss of stemness after only a few passages. One of the most interesting aspects of this study was the integration of factors in the culture conditions, which to some extent, mimicked the in vivo microenvironmental niche of the BMSCs. A number of studies have successfully established that the cellular niche is not an inert tissue component but is of prime importance. The total sum of stimuli from the microenvironment underpins the complex interplay of regulatory mechanisms which control multiple functions in stem cells most importantly stem cell renewal. Therefore, well characterised factors which affect BMSCs characteristics, such as fibronectin (FN) coating, and morphogens such as FGF2 and BMP4, were incorporated into the cell culture conditions. The experimental set up was designed to provide insight into the expression pattern of the stem cell related transcription factors Sox2, cMyc and Oct4, in BMSCs with respect to passaging and changes in culture conditions. Induction of these pluripotency markers in somatic cells by retroviral transfection has been shown to confer pluripotency and an ESCs like state. Our study demonstrated that all treatments could transiently induce the expression of Sox2, cMyc and Oct4, and favourably affect the proliferation potential of BMSCs. The combined effect of these treatments was able to induce and retain the endogenous nuclear expression of stem cell transcription factors in BMSCs over an extended number of in vitro passages. Our results therefore suggest that the transient induction and manipulation of endogenous expression of transcription factors critical for stemness can be achieved by modulating the culture conditions; the benefit of which is to circumvent the need for genetic manipulations. In summary, this study has explored the role of BMSCs in the diseased state of osteoarthritis, by employing transcriptional profiling along with SI. In particular this study pioneered the use of primary cells for generating novel antibodies by SI. We established that somatic cells and BMSCs have a basal level of expression of pluripotency markers. Furthermore, our study indicates that intrinsic signalling mechanisms of BMSCs are intimately linked with extrinsic cues from the microenvironment and that these signals appear to be critical for retaining the expression of genes to maintain cell stemness in long term in vitro culture. This project provides a basis for developing an “artificial niche” required for reversion of commitment and maintenance of BMSC in their uncommitted homeostatic state.
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VECELLIO, MATTEO LUCA. "Differentiation and reprogrammig of human mesenchymal stromal cells: insights from epigenetic assessments and pre-clinical studies." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2012. http://hdl.handle.net/10281/30253.

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Mesenchymal stromal cells (StC) are cells with plastic properties virtually present in every adult tissue. Recently, StC have also been isolated from adult human cardiac tissue (CStC) and the hypothesis has been raised that StC deriving from the heart may be genetically committed to cardiovascular differentiation. In this light, the enhancement of CStC cardiovascular precursor properties may represent a potentially successful strategy for cardiac regeneration purposes. Although of adult origin, CStC exhibit Islet1 expression and respond to chemically-determined cardiogenic epigenetic stimuli. Specifically we created an epigenetic chemical cocktail (EpiC)that is able to up-regulate the expression of cardiac resident stem cell markers c-Kit and MDR-1, together with the expression of a large number of cardiovascular-associated genes and regulatory RNAs including c-Kit, MDR-1, KDR, GATA6, Nkx2.5, GATA4, HCN4, NaV1.5, ALPHA-MHC, Alpha-sarcomeric actin, miR-1 and miR-499. Remarkably, EpiC-treated CStC also exhibited immature electrophysiological properties. Mechanistically, the EpiC treatment determined genome-wide histone modifications associated with a transcriptionally competent chromatin. Chromatin immunoprecipitation experiments (Chip) revealed that permissive histone modification H3K4Me3 was present in c-Kit, MDR-1 and Nkx2.5 promoter regions, possibly contributing to their expression. Altogether these data indicate that Isl1+ CStC may be epigenetically reprogrammed to acquire functionally competent cardiovascular precursor properties. CStC therefore appear as a potentially useful cell type for potential cardiac and vascular reconstructive therapies
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Atashpazgargari, S. "A CELL REPROGRAMMING-BASED APPROACH TO STUDY 7Q11.23 GENE DOSAGE IMBALANCES IN WILLIAMS BEUREN SYNDROME AND AUTISM SPECTRUM DISORDER." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/264765.

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Symmetrical gene dosage imbalances at 7q11.23 chromosomal region cause two unique neurodevelopmental diseases, Williams Beuren Syndrome (WBS) and the 7q11.23 microduplication associated to autistic spectrum disorder (7dup-ASD). Although both these diseases share common features such as intellectual disability and craniofacial dysmorphism, they can be distinguished by distinct social and language abilities: WBS patients characterized by hypersociality and comparatively well-preserved language skills while 7dup-ASD is associated with impairment in social interaction and communicative skills. The involvement of same genetic interval in these disease, points out to small subset of dosage-sensitive genes affecting cognition, social behavior and communication skills. Among the genes in the deleted region, some were shown to contribute to the abnormalities in these patients through transgenic mice models and individual case reports. However, the precise cellular and molecular phenotypes associated with these syndromes in disease-relevant cell-types are unknown due to the scarce availability of primary diseased tissues. Transcription factor induced somatic cell reprogramming has bypassed such fundamental limitation and has enabled us to model human diseases, elucidate their pathogenesis and discover new therapeutics by screening small chemicals/drugs on these models. During my PhD studies, I focused on the functional dissection of these complementary diseases at the level of transcriptional deregulation in patient-derived iPSC and its differentiated derivatives such as neural crest stem cells, mesenchymal stem cells, and neural progenitors. To this end, we have assembled a unique cohort of typical WBS, atypical WBS (patient with a partial deletion) and 7dup-ASD patients (along with unaffected relatives), and then I used mRNA reprogramming to establish and characterize at least 3 independent iPSC lines from a total of 12 individuals. High throughput mRNA sequencing on iPSC revealed critical transcriptional derangements in disease-relevant pathways already at the pluripotent state. These alterations found to be selectively amplified upon differentiation into disease-relevant lineages, thereby establishing the value of large iPSC cohorts in the elucidation of disease-relevant developmental pathways. Finally, we created an open-access web-based platform to make accessible our multi-layered datasets and integrate contributions by the entire community working on the molecular dissection of the 7q11.23 syndromes.
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Kennea, Nigel Leonard. "Neural differentiation of human fetal mesenchymal stem cells." Thesis, Imperial College London, 2007. http://hdl.handle.net/10044/1/7409.

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The potential of mesenchymal stem cells (MSC) to differentiate into neural lineages has raised the possibility of autologous cell transplantation as therapy for neurological diseases. There are, however, no studies reporting significant numbers of oligodendrocytes, the myelinforming cells of the central nervous system, derived from MSC. We have recently identified a population of circulating human fetal MSC that are highly proliferative and readily differentiate into bone, cartilage, fat and muscle. I demonstrated for the first time that primary fetal MSC differentiate into cells resemblifl neural precursors and then oligodendrocytes both in vitro and in vivo. By exposing cells to a neuronal conditioned medium, rates of oligodendrocyte differentiation approaching 50% were observed, and cells appeared to mature appropriately in culture. Importantly, the differentiation of a clonal population into both mesodermal (bone) and ectodermal (oligodendrocyte) lineages was achieved. In the developing murine brain, cells integrated but oligodendrocyte differentiation of naiVe fetal MSC was very low. The proportion of oligodendrocyte differentiation was increased (from 0.2% to 4%) by pre-exposing the cells to differentiation medium prior to transplantation. The process of in vivo differentiation occurred without cell fusion. Although the main focus of this thesis was oligodendrocyte differentiation, I also recapitulated controversial published work into neuronal differentiation of MSC. The exposure of cells to the reducing agent butylated hydroxyanisole induced rapid changes in cell morphology and expression of neuronal markers. These 'differentiated' cells did not, however, appear functional with no upregulation of voltage-gated sodium channels or synaptophysin. Finally, while stem cells offer promise for correction of brain diseases, one major obstacle is the poor survival of grafted cells. Investigation of apoptotic signalling showed fetal MSC have functional apoptotic machinery in both the intrinsic (mitochondrial) and extrinsic (death receptor) pathways which could be manipulated to prolong stem cell survival by inhibition of death signalling.
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Nicolaidou, Vicky. "Monocytes promote osteogenic differentiation of mesenchymal stem cells." Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/9061.

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Bone loss is a characteristic of many chronic inflammatory and degenerative diseases such as rheumatoid arthritis and osteoporosis. A major challenge is how to replace bone once it is lost. It is known that the immune system strongly regulates bone and investigations into these interactions have demonstrated that osteoclasts, the bone resorbing cells, are strongly regulated by the immune system. However, less is known about the regulation of osteoblasts, the bone forming cells. Mesenchymal stem cells are multipotent progenitors that can be induced in culture to form osteoblasts. The aim of this study was to investigate whether immune cells also regulate OB differentiation. Using in vitro cell cultures of human bone marrow-derived MSCs it was shown that monocytes/Mφs potently induced MSC differentiation to OBs evidenced by increased alkaline phosphatase and mineralisation. However, the ability of monocyte/Mφs to promote osteogenesis differed between CD14++CD16- and CD14+CD16+ monocyte subset as well as M-CSF and GM-CSF Mφs when activated; the CD16- monocytes and M-CSF Mφs still promoted differentiation whereas the CD16+ monocytes and GM-CSF Mφs inhibited it. The monocyte osteogenic effect was mediated by monocyte-derived soluble factors and required STAT3 signalling as well as COX2 upregulation and the production of PGE2. Finally, gene profiling microarray identified Oncostatin M as the mediator of monocyte-induced osteogenesis. This study established a role for monocyte/Mφs as critical regulators of osteogenic differentiation via OSM and STAT3 signalling. It also provides an insight into the interactions between MSCs and monocyte/Mφs in an inflammatory setting where OB differentiation will depend on the balance between pro-inflammatory versus anti-inflammatory monocyte/Mφs.
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Whyte, Jemima Lois. "Density dependent differentiation of mesenchymal stem cells to endothelial cells." Thesis, University of Manchester, 2010. https://www.research.manchester.ac.uk/portal/en/theses/density-dependent-differentiation-of-mesenchymal-stem-cells-to-endothelial-cells(d839ac9d-3bda-46fb-8e8e-556a85772db9).html.

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The differentiation of mesenchymal stem cells (MSCs) to endothelium is a critical but poorly understood feature of tissue vascularisation and considerable scepticism still remains surrounding this important differentiation event. Defining features of endothelial cells (ECs) are their ability to exist as contact-inhibited polarised monolayers that are stabilised by intercellular junctions, and the expression and activity of endothelial markers. During vasculogenesis, communication between MSCs and differentiated ECs or vascular smooth muscle cells, or between MSCs themselves is likely to influence MSC differentiation. In this study, the possibility that cell density can influence MSC differentiation along the EC lineage was examined. High density plating of human bone marrow-derived MSCs induced prominent endothelial characteristics including cobblestone-like morphology, enhanced endothelial networks, acetylated-low density lipoprotein uptake, vascular growth and stimulated expression of characteristic endothelial markers. Mechanistically, this density-dependent process has been defined. Cell-cell contact-induced Notch signalling was a key initiating step regulating commitment towards an EC lineage, whilst VEGF-A stimulation was required to consolidate the EC fate. Thus, this study not only provides evidence that MSC density is an essential microenvironmental factor stimulating the in vitro differentiation of MSCs to ECs but also demonstrates that MSCs can be differentiated to a functional EC. Taken together, defining how these crucial MSC differentiation events are regulated in vitro, provides an insight into how MSCs differentiate to ECs during postnatal neovascularisation and an opportunity for the therapeutic manipulation of MSCs in vivo, enabling targeted modulation of neovascularisation in ischaemia, wound healing and tumourigenesis.
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Hardy, Steven Allan. "Mesenchymal stem cells as trophic mediators of neural differentiation." Thesis, Durham University, 2010. http://etheses.dur.ac.uk/524/.

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Intense excitement and optimism surrounds the rapidly-expanding field of stem cell research, owing to their high capacity for self-renewal and intrinsic ability to differentiate into mature cell lineages. Although it may be envisioned that embryonic stem cells will be of significantly greater therapeutic value than their adult stem cell counterparts, the use of embryonic stem cells is fraught with both technical and ethical challenges and, as such, significant impetus has been placed on adult stem cell-based research. In particular, mesenchymal stem cells (MSCs) present as exciting candidates for potential use in cellular therapies and tissue engineering strategies. MSCs are defined at the functional level in terms of their ability to differentiate into mesodermal derivatives such as bone and fat. However, this functional definition is evolving, and there is considerable evidence to suggest that MSCs have a key role within their niche involving the release and/or uptake of soluble factors and cytokines, significantly influencing the behaviour of other cell types within the niche. Both facets of MSC behaviour are valuable from a clinical perspective, and have been examined in the present thesis. The most obvious and realistically-achievable clinical application of MSCs at present is in the treatment of osseous and adipose tissue defects. However, before the use of MSCs in the clinic becomes more commonplace, it is crucial to gain a more comprehensive understanding of the complex molecular and cellular mechanism(s) by which MSCs commit to a given fate and undergo differentiation to produce mature, fully-functional derivatives. Much of our present knowledge is derived from studies performed on the highly unnatural, 2D environment of tissue culture plastic. The present study assessed the behaviour of MSCs cultured on AlvetexTM, a novel, 3D scaffold manufactured by ReInnervate, with particular emphasis on the ability of MSCs to undergo osteogenic and adipogenic differentiation. Results obtained suggest that AlvetexTM may provide a more realistic and physiologically-relevant system in which to study osteogenesis and adipogenesis, in a manner more pertinent to that which occurs in vivo. Furthermore, the ability of MSCs to influence the behaviour of other cell types via the release of trophic factors and cytokines was examined, with particular emphasis on the nervous system. An in vitro conditioned media model was developed in order to investigate the influence(s) of MSC-derived soluble factors/cytokines on neural development and plasticity, using the adult rat hippocampal progenitor cell (AHPC) line as a model system. Results obtained suggest that, under defined conditions, MSCs secreted a complement of soluble factors/cytokines that induce AHPCs to commit to and undergo astrogenesis. This effect was characterised at both the cellular and molecular level. The specific complement of bioactive factors secreted by MSCs has been investigated using a combination of targeted transcriptional profiling and shotgun proteomics, and several putative candidate factors have been identified for further investigation.
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Prosser, Amy. "Enhanced differentiation of mesenchymal stem cells for osteochondral constructs." Thesis, University of Nottingham, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.727949.

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Novel osteochondral repair tissue engineering strategies are investigating the use of a single scaffold, with a portion for osteogenic and chondrogenic differentiation, and a single cell source, most notably the mesenchymal stem cell, to facilitate osteochondral differentiation and repair in a single construct. However, this approach requires robust differentiation protocols to ensure that the correct balance of each cell type is produced and maintained. Techniques used to analyse osteogenic and chondrogenic differentiation are well established, but many of the current methods described are qualitative, based on imaging stained cells or sections under a microscope. To facilitate higher throughput screening of chondrogenic differentiation in human MSCs, a novel culture technique using V shaped 96 well plates has been developed combining three robust and quantitative assays. Additionally, two reporter cell lines have been developed that express luciferase under the control of an osteogenic (osteocalcin) or chondrogenic (col2a1) promoter in order to streamline differentiation assays. The use of growth factors to elicit differentiation is well established; with BMP-2 used to enhance osteogenic differentiation and TGF-61 used to enhance chondrogenic differentiation. However, there are several limitations of using growth factors in regenerative medicine and consequently, the use of growth factor mimics was investigated. Two promising growth factor mimics were identified that could support both osteogenic and chondrogenic differentiation; LE135 and imperatorin. LE135, a retinoic acid receptor antagonist, significantly enhanced chondrogenesis with increased GAG production, col2a1 promoter activity and versican mRNA expression and had no significant effect on osteogenic differentiation. Imperatorin, a coumarin derivative, significantly enhanced early stage osteogenesis (alkaline phosphatase activity) and had no significant effect on late stage osteogenesis (mineralisation). Furthermore, chondrogenic differentiation was enhanced by imperatorin with significantly increased GAG production.
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Karageorgiou, Vassilis. "Bioinductive protein-based scaffolds for human mesenchymal stem cells differentiation /." Thesis, Connect to Dissertations & Theses @ Tufts University, 2004.

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Thesis (Ph. D.)--Tufts University, 2004.
Adviser: David L. Kaplan. Submitted to the Dept. of Chemical and Biological Engineering. Includes bibliographical references. Access restricted to members of the Tufts University community. Also available via the World Wide Web;
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Cameron, Katherine Rachel. "Calcium phosphate substrate-directed osteogenic differentiation of mesenchymal stem cells." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8051.

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An increase in degenerative bone disease in an ageing population, combined with a rise in the number of patients suffering from bone defects caused by physical trauma, makes the repair of bone an issue of growing clinical relevance. Current treatments such as autografts and allografts have major drawbacks, including donor site morbidity, limited availability, disease transmission and immune rejection. To overcome these issues synthetic bone grafts have been developed to mimic the mineral phase of bone. Given the significant roles of silicon in bone growth and development there has been great interest in introducing silicon into synthetic bone grafts to enhance their bioactivity. Calcium phosphate based silicate containing grafts have demonstrated enhanced bioactivity, improved physical properties, enhanced protein adsorption and greater bone formation, when compared to non-silicated calcium phosphates such as hydroxyapatite. However, is not clear whether the increased bone formation associated with these materials is the result of greater osteoblast activity or a rise in numbers of osteoblasts resulting from activation and differentiation of stem/ progenitor cells. To answer this question, multipotent stem cells were cultured on silicate substituted calcium phosphate (Si-CaP) and hydroxyapatite (HA). Si-CaP promoted greater cell adhesion and enhanced proliferation when compared to HA. Cells differentiated along the osteogenic lineage on both substrates as evidenced by up regulation of osteoblast specific genes and proteins. However, cells on Si-CaP showed earlier and greater gene expression of all osteoblast genes examined, and greater protein production as detected by immunohistochemistry. Integrin gene expression analysis revealed up regulation of α an d β subunits on both substrates during differentiation. Integrins α5 and β1 expression were greater on Si-CaP than on HA, suggesting preferential binding of fibronectin. The implication of these findings for tissue engineering is clear, suggesting these substrates may be utilized to control stem cell fate in vivo and in vitro without the need for osteogenic supplementation. Furthermore, the increased rate of differentiation seen on Si-CaP may enable the development of novel substrates for osteogenic differentiation of MSC, which may have significant impact in regenerative medicine.
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Books on the topic "Mesenchymal stem cells, reprogramming, differentiation"

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An, Chʻi-yŏng. Chungganyŏp chulgi sepʻo ŭi pʻumjil pʻyŏngka kijun e kwanhan yŏnʼgu: Punhwanŭng sinsok hwaginpŏp ŭi sŏlchŏng kanŭngsŏng tʻamsaek = A study on evaluation criteria for quality of mesenchymal stem cells : Investigation of the possibility to rapidly identify a differentiation potential. [Seoul]: Sikpʻum Ŭiyakpʻum Anjŏnchʻŏng Saengmul Ŭiyakpʻum Ponbu Sepʻo Chojik Konghak Chejetʻim, 2007.

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Nat, Roxana, and Andreas Eigentler. Cell Culture, iPS Cells and Neurodegenerative Diseases. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190233563.003.0013.

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Somatic reprogramming technology, which enables the conversion of adult human non-neural cells into neurons, has progressed rapidly in recent years. The derivation of patient-specific induced pluripotent stem (iPS) cells has become routine. The inherent broad differentiation potential of iPS cells makes possible the generation of diverse types of human neurons. This constitutes a remarkable step in facilitating the development of more appropriate and comprehensive preclinical human disease models, as well as for high throughput drug screenings and cell therapy. This chapter reviews recent progress in the human iPS cell culture models related to common and rare NDDs, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, spinal muscular atrophy, and degenerative ataxias. It focuses on the pathophysiological features revealed in cell cultures, and the neuronal subtypes most affected in NDDs. The chapter discusses the validity, limitation, and improvements of this system in faithfully and reproducibly recapitulating disease pathology.
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Reader, Jocelyn, Sarah Lynam, Amy Harper, Gautam Rao, Maya Matheny, and Dana M. Roque. Ovarian Tumor Microenvironment and Innate Immune Recognition. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190248208.003.0004.

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Ovarian adenocarcinoma is typified by detection at late stages with dissemination of cancer cells into the peritoneal cavity and frequent acquisition of chemoresistance. A number of studies show the importance of the tumor microenvironment and innate immune recognition in tumor progression. Ovarian cancer cells can regulate the composition of their stroma to promote the formation of ascitic fluid rich in cytokines and bioactive lipids such as PGE2, and to stimulate the differentiation of stromal cells into a pro-tumoral phenotype. In response, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, tumor-associated macrophages, and other peritoneal cells can act through direct and indirect mechanisms to regulate tumor growth, chemoresistance via alteration of class III β‎ tubulin, angiogenesis and dissemination. This chapter deciphers the current knowledge about the role of stromal cells, associated secreted factors, and the immune system on tumor progression. This suggests that targeting the microenvironment holds great potential to improve the prognosis of patients with ovarian adenocarcinoma.
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Book chapters on the topic "Mesenchymal stem cells, reprogramming, differentiation"

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Reger, Roxanne L., Alan H. Tucker, and Margaret R. Wolfe. "Differentiation and Characterization of Human MSCs." In Mesenchymal Stem Cells, 93–107. Totowa, NJ: Humana Press, 2008. http://dx.doi.org/10.1007/978-1-60327-169-1_7.

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Leu, Yu-Wei, Tim H. M. Huang, and Shu-Huei Hsiao. "Epigenetic Reprogramming of Mesenchymal Stem Cells." In Advances in Experimental Medicine and Biology, 195–211. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-9967-2_10.

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Lian, Qizhou, Yuelin Zhang, Xiaoting Liang, Fei Gao, and Hung-Fat Tse. "Directed Differentiation of Human-Induced Pluripotent Stem Cells to Mesenchymal Stem Cells." In Mesenchymal Stem Cells, 289–98. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3584-0_17.

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deCarvalho, Ana C., and Tom Mikkelsen. "Gliosarcoma Stem Cells: Glial and Mesenchymal Differentiation." In Stem Cells and Cancer Stem Cells, Volume 2, 75–81. Dordrecht: Springer Netherlands, 2011. http://dx.doi.org/10.1007/978-94-007-2016-9_8.

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Ciuffreda, Maria Chiara, Giuseppe Malpasso, Paola Musarò, Valentina Turco, and Massimiliano Gnecchi. "Protocols for in vitro Differentiation of Human Mesenchymal Stem Cells into Osteogenic, Chondrogenic and Adipogenic Lineages." In Mesenchymal Stem Cells, 149–58. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3584-0_8.

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Ripoll, Cynthia B., and Bruce A. Bunnell. "Marrow Stromal Mesenchymal Stem Cells." In Cell Cycle Regulation and Differentiation in Cardiovascular and Neural Systems, 121–38. New York, NY: Springer New York, 2010. http://dx.doi.org/10.1007/978-1-60327-153-0_7.

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Lu, Shi-Jiang, Qiang Feng, Jennifer S. Park, and Robert Lanza. "Directed Differentiation of Red Blood Cells from Human Embryonic Stem Cells." In Cellular Programming and Reprogramming, 105–21. Totowa, NJ: Humana Press, 2010. http://dx.doi.org/10.1007/978-1-60761-691-7_7.

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Cook, David, and Paul Genever. "Regulation of Mesenchymal Stem Cell Differentiation." In Transcriptional and Translational Regulation of Stem Cells, 213–29. Dordrecht: Springer Netherlands, 2013. http://dx.doi.org/10.1007/978-94-007-6621-1_12.

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Vidal, Martin A., and Mandi J. Lopez. "Adipogenic Differentiation of Adult Equine Mesenchymal Stromal Cells." In Adipose-Derived Stem Cells, 61–75. Totowa, NJ: Humana Press, 2010. http://dx.doi.org/10.1007/978-1-61737-960-4_6.

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Chung, Tze Wen, and Ming-Chia Yang. "Rat Mesenchymal Cell CD44 Surface Markers: Role in Cardiomyogenic Differentiation." In Stem Cells and Cancer Stem Cells, Volume 2, 185–90. Dordrecht: Springer Netherlands, 2011. http://dx.doi.org/10.1007/978-94-007-2016-9_19.

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Conference papers on the topic "Mesenchymal stem cells, reprogramming, differentiation"

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Miyazaki, Yoshihiro, Yutato Kumagai, Hiroko Kushige, Osamu Shimomura, Yasuyuki Kida, and Tatsuya Oda. "Abstract A32: Adipose-derived mesenchymal stem cell has the differentiation/reprogramming capacity towards two distinct cancer-associated fibroblasts." In Abstracts: AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; September 6-9, 2019; Boston, MA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.panca19-a32.

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Moussi, Khalil, Dina B. Abusamra, Omar Yassine, Jasmeen Merzaban, and Jurgen Kosel. "Strain-induced Differentiation of Mesenchymal Stem Cells." In 2020 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) in conjunction with the 43rd Annual Conference of the Canadian Medical and Biological Engineering Society. IEEE, 2020. http://dx.doi.org/10.1109/embc44109.2020.9176273.

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Shu, K., H. Thatte, and M. Spector. "Chondrogenic differentiation of adult mesenchymal stem cells and embryonic stem cells." In 2009 IEEE 35th Annual Northeast Bioengineering Conference. IEEE, 2009. http://dx.doi.org/10.1109/nebc.2009.4967739.

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Walker, NM, LN Badri, T. Ohtsuka, VJ Thannickal, A. Flint, and VN Lama. "Fibrotic Differentiation Potential of Lung Resident Mesenchymal Stem Cells." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a3680.

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Billing, Anja M., Shaima S. Dib, Hisham Ben Hamidane, Neha Goswami, Rasha Al-mismar, Richard Cotton, Pankaj Kumar, et al. "Comprehensive Characterization Of The Differentiation Of Human Embryonic Stem Cells Into Mesenchymal Stem Cells." In Qatar Foundation Annual Research Conference Proceedings. Hamad bin Khalifa University Press (HBKU Press), 2014. http://dx.doi.org/10.5339/qfarc.2014.hbpp0979.

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Parveen, Asma, David Mills, Debasish Kuila, and Debasish Kuila. "Porous silicon substrates support osteogenic differentiation of mesenchymal stem cells." In 2016 International Conference on Systems in Medicine and Biology (ICSMB). IEEE, 2016. http://dx.doi.org/10.1109/icsmb.2016.7915105.

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Lee, Sue Hyun, Angela L. Zachman, Desirae L. Deskins, Pampee P. Young, and Hak-Joon Sung. "ROS-Responsive Scaffold for Angiogenic Differentiation of Mesenchymal Stem Cells." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14553.

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Vascularization of a tissue-engineered construct enables efficient transport of nutrients and waste products; it is necessary for successful long-term tissue growth and host integration. Although significant progress has been made, sufficient vascularization of engineered constructs is still a major challenge, limiting clinical applications of tissue engineering (TE) approaches [1]. Successful vascularization promotes the interactions of TE implants with host tissues, leading to efficient tissue regeneration. Therefore, there is an unmet need to develop a more efficient method to vascularize TE constructs. In particular, obtaining a reliable source of endothelial cells (ECs) that line all blood vessels is a critical and challenging step towards successful vascularization of TE constructs, empowering TE to be applied in a larger scale and scope.
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Engler, Adam J. "Probing Mechanisms of Mechano-Sensitive Differentiation in Mesenchymal Stem Cells." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19184.

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Adult mesenchymal stem cells (MSCs) have recently been shown to be responsive to the properties of their adjacent extracellular niche, most notably physical parameters such as topography and elasticity. Elasticity varies dramatically between tissues that MSCs inhibit, which drives elasticity-based differentiation into neurons, muscle, bone, etc. However within tissues, distinct elasticity gradients, brought on by pathological conditions, e.g. myocardial infarction ∼ 8.67 ± 1.50 kPa/mm, or through normal tissue variation, e.g. 0.58 ± 0.88 kPa/mm, could drive MSC migration. In fact, MSCs appear to undergo directed migration up elasticity gradients, or “durotax,” as shallow as 0.96 kPa/mm, indicating a ‘differentiation hierarchy’ since when given the choice, MSCs will durotax into the stiffest regions of the niche and then differentiate based on niche elasticity. As cells move up the gradient, they do so by deforming their niche to determine it’s elasticity, but the molecular mechanism that converts this biophysical signal into a biochemical one which the nucleus can interpret is yet unresolved. We have identified several focal adhesion-related proteins may be capable of force-induced conformational changes, e.g. vinculin. Upon the application of different amounts of traction stress in situ by MSCs, an appropriate amount of stretching results in the exposure of cryptic MAPK binding sites within vinculin and suggests that vinculin, among other focal adhesion proteins, may be sensitive to physical ECM properties and thus able to relay information leading to differentiation of stem cells.
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Chen, Jing, and Sihong Wang. "Thermal Effects on Osteogenesis of Human Mesenchymal Stem Cells." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80885.

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Intensive studies were reported on the osteogenesis of mesenchymal stem cells (MSC) using chemicals and mechanical loading. However, the maturity of differentiated osteoblasts is not same as that of isolated adult osteoblasts. Thermal treatment could be a missing factor in stem cell differentiation. It was reported that mild heat stimulated bone growth in animal experiments [1–2]. Thermal treatment is also used as a therapy to promote bone repair after injury [3]. In addition, hot shower daily is recommended to osteoarthritis patients. However, the mechanisms for the heat-induced osteogenesis are not completely known and the thermal regulation of human mesenchymal stem cells (hMSCs) differentiation is not well studied. In this study, the direct effects of mild heat shock (HS) on the differentiation of hMSCs into osteoblasts in self-assembling peptide hydrogel were investigated.
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Tanaka, Nobuyuki, Tadahiro Yamashita, Viola Vogel, and Yo Tanaka. "Agarose micro-cast for the patterned differentiation of mesenchymal stem cells." In 2016 International Symposium on Micro-NanoMechatronics and Human Science (MHS). IEEE, 2016. http://dx.doi.org/10.1109/mhs.2016.7824184.

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