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Journal articles on the topic 'Cell niche'

Author: Grafiati

Published: 24 April 2022

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1

Ema, Hideo, and Toshio Suda. "Two anatomically distinct niches regulate stem cell activity." Blood 120, no. 11 (September 13, 2012): 2174–81. http://dx.doi.org/10.1182/blood-2012-04-424507.

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Abstract The niche microenvironment controls stem cell number, fate, and behavior. The bone marrow, intestine, and skin are organs with highly regenerative potential, and all produce a large number of mature cells daily. Here, focusing on adult stem cells in these organs, we compare the structures and cellular components of their niches and the factors they produce. We then define the niche as a functional unit for stem cell regulation. For example, the niche possibly maintains quiescence and regulates fate in stem cells. Moreover, we discuss our hypothesis that many stem cell types are regulated by both specialized and nonspecialized niches, although hematopoietic stem cells, as an exception, are regulated by a nonspecialized niche only. The specialized niche is composed of 1 or a few types of cells lying on the basement membrane in the epithelium. The nonspecialized niche is composed of various types of cells widely distributed in mesenchymal tissues. We propose that the specialized niche plays a role in local regulation of stem cells, whereas the nonspecialized niche plays a role in relatively broad regional or systemic regulation. Further work will verify this dual-niche model to understand mechanisms underlying stem cell regulation.

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2

Hayashi, Yoshiki, Satoru Kobayashi, and Hiroshi Nakato. "Drosophila glypicans regulate the germline stem cell niche." Journal of Cell Biology 187, no. 4 (November 9, 2009): 473–80. http://dx.doi.org/10.1083/jcb.200904118.

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Stem cells are maintained in vivo by short-range signaling systems in specialized microenvironments called niches, but the molecular mechanisms controlling the physical space of the stem cell niche are poorly understood. In this study, we report that heparan sulfate (HS) proteoglycans (HSPGs) are essential regulators of the germline stem cell (GSC) niches in the Drosophila melanogaster gonads. GSCs were lost in both male and female gonads of mutants deficient for HS biosynthesis. dally, a Drosophila glypican, is expressed in the female GSC niche cells and is responsible for maintaining the GSC niche. Ectopic expression of dally in the ovary expanded the niche area, showing that dally is required for restriction of the GSC niche space. Interestingly, the other glypican, dally-like, plays a major role in regulating male GSC niche maintenance. We propose that HSPGs define the physical space of the niche by serving as trans coreceptors, mediating short-range signaling by secreted factors.

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3

Chan, Charles, Ching-Cheng Chen, Daniel L. Kraft, Cynthia Luppen, Jae-Beom Kim, Anthony DeBoer, Kevin Wei Wei, and Irving L. Weissman. "Identification and Isolation of the Hematopoietic Stem Cell Niche Initiating Cell Population." Blood 112, no. 11 (November 16, 2008): 3574. http://dx.doi.org/10.1182/blood.v112.11.3574.3574.

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Abstract Introduction: Identification and understanding of the cells and processes that can generate, sustain and influence the HSC niche and hematopoiesis are critical for the development of a more comprehensive knowledge of normal hematopoiesis, stem cell homing, trafficking, differentiation and hematopoietic pathology. Growth and renewal in many tissues are initiated by stem cells, supported by the microenvironment (niche) in which they reside. While recent work has begun to describe functional interactions between stem cells and their niches, little is known about the formation of stem cell niches. Methods & Results: We established a functional, in vivo assay (via implantation of cells under the renal capsule) to isolate the determinants of hematopoietic stem cell (HSC) niche formation and activity. Using this novel assay, we show that a population of progenitor cells (CD45−Tie2-aV+CD105+Thy1.1−; CD105+Thy1−) sorted from 15.5 dpc fetal limbs and transplanted under the adult mouse renal capsule recruit host-derived vasculatures in a VEGF dependent manner, produce donor-derived ectopic bones through endochondral ossification, and generate a marrow cavity populated by host-derived long term reconstituting HSC (LT-HSC). In contrast, CD45−Tie2-aV+CD105+Thy1a+ (CD105+Thy1+) progenitors form bone that does not contain a marrow cavity. While analyzing these and other sorted populations, we did not observe any instances where niche was present without bone, suggesting that skeletal progenitors are necessary for initiating an HSC niche but osteoblasts alone cannot initiate and support niche activity. Suppression of factors important for HSC maintenance, such as steel factor (SLF), in progenitor populations prior to transplant did not alter their ability to initiate and support an HSC niche. On the other hand, suppression of factors involved in endochondral ossification, such as osterix and VEGF, inhibited niche generation. Furthermore, CD105+Thy1− progenitor populations derived from regions of the fetal mandible or calvaria that do not undergo endochondral ossification form only bone without marrow in our assay. Conclusions: In addition to identifying the limb-derived skeletal progenitor capable of endochondral ossification involved and the basic mechanisms of HSC niche initiation, our study provides a functional framework by which future studies on HSC-niche interactions at the cellular level can be carried out.

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4

Gulmez Sevim, Duygu, and Ugur Acar. "Stem Cell-Based Treatment Modalities for Limbal Stem Cell Deficiency." Niche Journal 2, no. 3 (February 9, 2015): 25–30. http://dx.doi.org/10.5152/niche.2014.166.

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5

Cakmak, Hasan Basri. "Corneal Endothelial Cell Sheaths: A New Avenue in Stem Cell Research?" Niche Journal 2, no. 3 (February 9, 2015): 31–35. http://dx.doi.org/10.5152/niche.2014.169.

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6

Sharma, Shilpa, and Gurudutta Gangenahalli. "Adult Hematopoietic Stem Cells: Niche Cross-Talks to Affect the Cell Fate." Niche Journal 3, no. 1 (January 6, 2016): 12–23. http://dx.doi.org/10.5152/niche.2015.215.

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7

Ozdemir, Aysun, and Mustafa Ark. "xCELLigence Real Time Cell Analysis System: A New Method for Cell Proliferation and Cytotoxicity." Niche Journal 2, no. 2 (September 12, 2014): 15–17. http://dx.doi.org/10.5152/niche.2014.153.

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8

Kandarakov, Oleg, Alexander Belyavsky, and Ekaterina Semenova. "Bone Marrow Niches of Hematopoietic Stem and Progenitor Cells." International Journal of Molecular Sciences 23, no. 8 (April 18, 2022): 4462. http://dx.doi.org/10.3390/ijms23084462.

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The mammalian hematopoietic system is remarkably efficient in meeting an organism’s vital needs, yet is highly sensitive and exquisitely regulated. Much of the organismal control over hematopoiesis comes from the regulation of hematopoietic stem cells (HSCs) by specific microenvironments called niches in bone marrow (BM), where HSCs reside. The experimental studies of the last two decades using the most sophisticated and advanced techniques have provided important data on the identity of the niche cells controlling HSCs functions and some mechanisms underlying niche-HSC interactions. In this review we discuss various aspects of organization and functioning of the HSC cell niche in bone marrow. In particular, we review the anatomy of BM niches, various cell types composing the niche, niches for more differentiated cells, metabolism of HSCs in relation to the niche, niche aging, leukemic transformation of the niche, and the current state of HSC niche modeling in vitro.

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9

Boulais, Philip E., and Paul S. Frenette. "Making sense of hematopoietic stem cell niches." Blood 125, no. 17 (April 23, 2015): 2621–29. http://dx.doi.org/10.1182/blood-2014-09-570192.

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Abstract The hematopoietic stem cell (HSC) niche commonly refers to the pairing of hematopoietic and mesenchymal cell populations that regulate HSC self-renewal, differentiation, and proliferation. Anatomic localization of the niche is a dynamic unit from the developmental stage that allows proliferating HSCs to expand before they reach the bone marrow where they adopt a quiescent phenotype that protects their integrity and functions. Recent studies have sought to clarify the complexity behind the HSC niche by assessing the contributions of specific cell populations to HSC maintenance. In particular, perivascular microenvironments in the bone marrow confer distinct vascular niches that regulate HSC quiescence and the supply of lineage-committed progenitors. Here, we review recent data on the cellular constituents and molecular mechanisms involved in the communication between HSCs and putative niches.

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10

Khlusov, Igor A., Larisa S. Litvinova, Marina Yu Khlusova, and Kristina A. Yurova. "Concept of Hematopoietic and Stromal Niches for Cell-Based Diagnostics and Regenerative Medicine (a Review)." Current Pharmaceutical Design 24, no. 26 (November 14, 2018): 3034–54. http://dx.doi.org/10.2174/1381612824666180829154119.

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Background: R. Schofield (1978) proposed a hypothesis of hematopoietic stem cells (HSCs) niche (specialized cell microenvironment). An existence of osteoblastic and vascular niches for HSCs has been postulated since 2003. At the same time, the discussion about the existence and functioning of niche for multipotent mesenchymal stromal cells (MMSCs) is just beginning to develop. The design of artificial materials capable of biomimetical reproductionof the cellular and tissue microenvironment based on ideas and main elements borrowed from wildlife is an experimental approach in search of the stem cell niches. Results: Recent attempts to model the microterritories (niches) for HSCs have been undertaken and the behavior of cells in such structures has been investigated. However, the main quantitative factors involved in the original design of stem cell microterritories remain unknown. At the modern stage, the topography, hierarchy, and the size of the niches have to be determined, because the definition of the niches as morphological (structural and functional) units (microterritories), which provides the conditions for vital activity of stem cells, implies finite values of its parameters. The aim of this review was the critical review of key milestones of the niche concept for HSCs and MMSCs as we understood it. Conclusion: We speculated our definition of the stem cell niche, proposed and described certain stages (postulation; morphofunctional; topographical; quantitative; bioengineering) of the niche theory development. Prospective directions of the niche designing for cell-based diagnostics and regenerative medicine were noted.

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11

Asada, Noboru, Yuya Kunisaki, Takashi Nagasawa, and Paul S. Frenette. "Distinct Contributions By Perivascular Niche Cells in Hematopoietic Stem Cell Maintenance." Blood 126, no. 23 (December 3, 2015): 661. http://dx.doi.org/10.1182/blood.v126.23.661.661.

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Abstract Hematopoietic stem cells (HSCs) self-renew and differentiate into all blood types in response to various demands through life. HSC functions are tightly and finely tuned by a specialized microenvironment called "niche" in the bone marrow (BM). Using Nestin-GFP transgenic mice, we have identified Nestin-GFP+ perivascular stromal cells exhibiting a mesenchymal stem/progenitor cell activity as niche cells. Furthermore, we found two types of Nestin-GFP+ cells expressing different surface markers, Nerve/glial antigen 2 (NG2) and Leptin receptor (Lepr) that are associated with arterioles and sinusoid, respectively, in the BM (Kunisaki et al. Nature, 2013). Both arteriolar and sinusoidal niche cells have been reported to show high gene expression of cytokines essential for HSC maintenance such as CXCL12 and stem cell factor (SCF), however, it remains unknown how the distinct niche cells differentially regulate HSC functions. To investigate the mechanisms, we utilized genetic mouse models, in which CXCL12 or SCF can be deleted in specific cell types. CXCL12 deletion in sinusoidal niche cells by using Lepr-cre/Cxcl12fl/− mice mobilized HSCs and lineage− Sca-1+ c-kit+ (LSK) progenitors into spleen (HSC, CT: Control/DL: Deleted: 760±165 / 2193±557 / spleen, n=6, p<0.05) and blood (LSK, CT/DL: 177±36 / 668±156 / mL blood, n=5, p<0.05), but had no effect on HSC numbers in the BM (CT/DL: 1435±101 / 1194±75 / femur, n=6, p=0.085), which is consistent with a previous report (Ding and Morrison, Nature, 2013). Furthermore, assessments of endogenous HSC localization using whole-mount 3D imaging technology revealed that the deletion of CXCL12 in Lepr+ niche cells had no impact on HSC location (KS-test: Two-sample Kolmogorov-Smirnov test, p=0.9981). By contrast, deletion of CXCL12 in NG2-cre derived cells, which recombines efficiently in the entire Nestin-GFP+ non-endothelial stromal fraction including both peri-arteriolar and peri-sinusoidal cells (96.9±1.3%), and overlapping with Lepr+ cells (88.5±1.6%) and CXCL12-abundant reticular cells (90.7±1.4%), led to a robust reduction of HSC numbers in the BM (CT/DL: 1487±87 / 179±40 / femur, n=10, p<0.0001) with HSC and progenitor mobilization into spleen (HSC, CT/DL: 705±262 / 3550±540 / spleen, n=6-8, p<0.01) and blood (LSK, CT/DL: 494±178 / 5357±896 / mL blood, n=5-7, p<0.01). In addition, deletion of CXCL12 in NG2-cre targeted cells led to HSC displacement away from arterioles (KS-test: Two-sample Kolmogorov-Smirnov test; p=0.001). To examine further a role of CXCL12 produced by NG2+ arteriolar niches on HSC maintenance, we generated tamoxifen-inducible NG2-creERTM/Cxcl12fl/− mice. Deletion of CXCL12 postnatally in NG2+ arteriolar niche cells significantly reduced the number of HSCs in the BM (CT/DL: 1617±160 / 960±95 / femur, n=10-13, p=0.0013), which was confirmed functionally by a competitive repopulation assay. Moreover, 3D imaging revealed that HSCs were located further away from arterioles in NG2-creERTM/Cxcl12fl/− marrow (KS-test: p<0.0001), suggesting a role for arteriolar niches in CXCL12-mediated HSC maintenance. As niche cells synthesize several factors, we evaluated the contribution of arteriolar niches in SCF synthesis, a cytokine shown to be critical for HSC maintenance. As expected, deletion of SCF in NG2-cre targeted cells led to a significant reduction of HSC numbers in the BM (CT/DL: 606±85 / 96±23 / femur, n=5-7, p<0.0001). To further evaluate functions of SCF produced by distinct vascular niches, we also compared these mice with deletions using Lepr-cre or tamoxifen-inducible NG2-creERTM mice. We found that deletion of SCF in Lepr-cre targeted cells showed a significant reduction of HSC numbers in the BM (CT/DL: 690±84 / 220±83 / femur, n=3-4, p<0.0118), consistent with previous studies (Ding et al., Nature, 2012), whereas there was no significant change observed in NG2-creERTM/SCFfl/− mice, suggesting that Lepr+ vascular niches rather than NG2+ arteriolar niches are the most important source of SCF in the BM. These results highlight distinct contributions of perivascular cells primarily located in separate vascular niches, arteriolar and sinusoidal, in HSC maintenance and mobilization. Disclosures No relevant conflicts of interest to declare.

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12

Yu, Zhuo, Wenqian Yang, Xiaoxiao He, Chiqi Chen, Wenrui Li, Limin Zhao, Ligen Liu, et al. "Endothelial cell-derived angiopoietin-like protein 2 supports hematopoietic stem cell activities in bone marrow niches." Blood 139, no. 10 (March 10, 2022): 1529–40. http://dx.doi.org/10.1182/blood.2021011644.

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Abstract Bone marrow niche cells have been reported to fine-tune hematopoietic stem cell (HSC) stemness via direct interaction or secreted components. Nevertheless, how niche cells control HSC activities remains largely unknown. We previously showed that angiopoietin-like protein 2 (ANGPTL2) can support the ex vivo expansion of HSCs by binding to human leukocyte immunoglobulin-like receptor B2. However, how ANGPTL2 from specific niche cell types regulates HSC activities under physiological conditions is still not clear. Herein, we generated an Angptl2-flox/flox transgenic mouse line and conditionally deleted Angptl2 expression in several niche cells, including Cdh5+ or Tie2+ endothelial cells, Prx1+ mesenchymal stem cells, and Pf4+ megakaryocytes, to evaluate its role in the regulation of HSC fate. Interestingly, we demonstrated that only endothelial cell-derived ANGPTL2 and not ANGPTL2 from other niche cell types plays important roles in supporting repopulation capacity, quiescent status, and niche localization. Mechanistically, ANGPTL2 enhances peroxisome-proliferator-activated receptor D (PPARD) expression to transactivate G0s2 to sustain the perinuclear localization of nucleolin to prevent HSCs from entering the cell cycle. These findings reveal that endothelial cell-derived ANGPTL2 serves as a critical niche component to maintain HSC stemness, which may benefit the understanding of stem cell biology in bone marrow niches and the development of a unique strategy for the ex vivo expansion of HSCs.

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13

Oatley, Jon M., and Ralph L. Brinster. "The Germline Stem Cell Niche Unit in Mammalian Testes." Physiological Reviews 92, no. 2 (April 2012): 577–95. http://dx.doi.org/10.1152/physrev.00025.2011.

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This review addresses current understanding of the germline stem cell niche unit in mammalian testes. Spermatogenesis is a classic model of tissue-specific stem cell function relying on self-renewal and differentiation of spermatogonial stem cells (SSCs). These fate decisions are influenced by a niche microenvironment composed of a growth factor milieu that is provided by several testis somatic support cell populations. Investigations over the last two decades have identified key determinants of the SSC niche including cytokines that regulate SSC functions and support cells providing these factors, adhesion molecules that influence SSC homing, and developmental heterogeneity of the niche during postnatal aging. Emerging evidence suggests that Sertoli cells are a key support cell population influencing the formation and function of niches by secreting soluble factors and possibly orchestrating contributions of other support cells. Investigations with mice have shown that niche influence on SSC proliferation differs during early postnatal development and adulthood. Moreover, there is mounting evidence of an age-related decline in niche function, which is likely influenced by systemic factors. Defining the attributes of stem cell niches is key to developing methods to utilize these cells for regenerative medicine. The SSC population and associated niche comprise a valuable model system for study that provides fundamental knowledge about the biology of tissue-specific stem cells and their capacity to sustain homeostasis of regenerating tissue lineages. While the stem cell is essential for maintenance of all self-renewing tissues and has received considerable attention, the role of niche cells is at least as important and may prove to be more receptive to modification in regenerative medicine.

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14

Feyat, Mehmet Sedat, Sercan Mercan, Emrullah Calisir, Gulbahar Boyuk, Ferda Alpaslan Pinarli, Ahmet Yesilyurt, Ersin Fadillioglu, and Tuncay Delibasi. "Pancreatic Beta Cell Purification by Flow Cytometer and a Modified Rat Pancreatic Islet Cell Isolation Method." Niche Journal 3, no. 1 (January 6, 2016): 1–8. http://dx.doi.org/10.5152/niche.2015.216.

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15

Scadden, David T. "Nice Neighborhood: Emerging Concepts of the Stem Cell Niche." Cell 157, no. 1 (March 2014): 41–50. http://dx.doi.org/10.1016/j.cell.2014.02.013.

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16

Polisetti, Naresh, Matthias Zenkel, Johannes Menzel-Severing, Friedrich E. Kruse, and Ursula Schlötzer-Schrehardt. "Cell Adhesion Molecules and Stem Cell-Niche-Interactions in the Limbal Stem Cell Niche." STEM CELLS 34, no. 1 (September 11, 2015): 203–19. http://dx.doi.org/10.1002/stem.2191.

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17

Shrestha, Kshitiz Raj, and So Young Yoo. "Phage-Based Artificial Niche: The Recent Progress and Future Opportunities in Stem Cell Therapy." Stem Cells International 2019 (April 3, 2019): 1–14. http://dx.doi.org/10.1155/2019/4038560.

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Self-renewal and differentiation of stem cells can be the best option for treating intractable diseases in regenerative medicine, and they occur when these cells reside in a special microenvironment, called the “stem cell niche.” Thus, the niche is crucial for the effective performance of the stem cells in bothin vivoandin vitrosince the niche provides its functional cues by interacting with stem cells chemically, physically, or topologically. This review provides a perspective on the different types of artificial niches including engineered phage and how they could be used to recapitulate or manipulate stem cell niches. Phage-based artificial niche engineering as a promising therapeutic strategy for repair and regeneration of tissues is also discussed.

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18

Nimiritsky, P. P., G. D. Sagaradze, A. Yu Efimenko, P. I. Makarevich, and V. A. Tkachuk. "THE STEM CELL NICHE." Tsitologiya 60, no. 8 (2018): 575–86. http://dx.doi.org/10.31116/tsitol.2018.08.01.

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19

VanHook, A. M. "DIY Stem Cell Niche." Science Signaling 6, no. 305 (December 10, 2013): ec297-ec297. http://dx.doi.org/10.1126/scisignal.2004976.

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20

Walker, MR, KK Patel, and TS Stappenbeck. "The stem cell niche." Journal of Pathology 217, no. 2 (January 2009): 169–80. http://dx.doi.org/10.1002/path.2474.

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21

Hira, Vashendriya V. V., Jill R. Wormer, Hala Kakar, Barbara Breznik, Britt van der Swaan, Renske Hulsbos, Wikky Tigchelaar, et al. "Periarteriolar Glioblastoma Stem Cell Niches Express Bone Marrow Hematopoietic Stem Cell Niche Proteins." Journal of Histochemistry & Cytochemistry 66, no. 3 (January 3, 2018): 155–73. http://dx.doi.org/10.1369/0022155417749174.

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In glioblastoma, a fraction of malignant cells consists of therapy-resistant glioblastoma stem cells (GSCs) residing in protective niches that recapitulate hematopoietic stem cell (HSC) niches in bone marrow. We have previously shown that HSC niche proteins stromal cell–derived factor-1α (SDF-1α), C-X-C chemokine receptor type 4 (CXCR4), osteopontin (OPN), and cathepsin K (CatK) are expressed in hypoxic GSC niches around arterioles in five human glioblastoma samples. In HSC niches, HSCs are retained by binding of SDF-1α and OPN to their receptors CXCR4 and CD44, respectively. Protease CatK cleaves SDF-1α to release HSCs out of niches. The aim of the present study was to reproduce the immunohistochemical localization of these GSC markers in 16 human glioblastoma samples with the addition of three novel markers. Furthermore, we assessed the type of blood vessels associated with GSC niches. In total, we found seven GSC niches containing CD133-positive and nestin-positive GSCs as a single-cell layer exclusively around the tunica adventitia of 2% of the CD31-positive and SMA-positive arterioles and not around capillaries and venules. Niches expressed SDF-1α, CXCR4, CatK, OPN, CD44, hypoxia-inducible factor-1α, and vascular endothelial growth factor. In conclusion, we show that GSC niches are present around arterioles and express bone marrow HSC niche proteins.

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Mathur, Divya, Alyssa Bost, Ian Driver, and Benjamin Ohlstein. "A Transient Niche Regulates the Specification of Drosophila Intestinal Stem Cells." Science 327, no. 5962 (January 7, 2010): 210–13. http://dx.doi.org/10.1126/science.1181958.

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Stem cell niches are locations where stem cells reside and self-renew. Although studies have shown how niches maintain stem cell fate during tissue homeostasis, less is known about their roles in establishing stem cells. The adult Drosophila midgut is maintained by intestinal stem cells (ISCs); however, how they are established is unknown. Here, we show that an ISC progenitor generates a niche cell via Notch signaling. This niche uses the bone morphogenetic protein 2/4 homolog, decapentaplegic, to allow progenitors to divide in an undifferentiated state and subsequently breaks down and dies, resulting in the specification of ISCs in the adult midgut. Our results demonstrate a paradigm for stem cell–niche biology, where progenitors generate transient niches that determine stem cell fate and may give insights into stem cell specification in other tissues.

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Wang, Liwei, Zhouhua Li, and Yu Cai. "The JAK/STAT pathway positively regulates DPP signaling in the Drosophila germline stem cell niche." Journal of Cell Biology 180, no. 4 (February 18, 2008): 721–28. http://dx.doi.org/10.1083/jcb.200711022.

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The stem cell niche, formed by surrounding stromal cells, provides extrinsic signals that maintain stem cell self-renewal. However, it remains unclear how these extrinsic signals are regulated. In the Drosophila female germline stem cell (GSC) niche, Decapentaplegic (DPP) is an important niche factor for GSC self-renewal. The exact source of the DPP and how its transcription is regulated in this niche remain unclear. We show that dpp is expressed in somatic cells of the niche including the cap cells, a subtype of niche cells. Furthermore, our data show that the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway positively regulates dpp expression in the cap cells, suggesting that JAK/STAT activity is required in somatic niche cells to prevent precocious GSC differentiation. Our data suggest that the JAK/STAT pathway functions downstream/independently of cap cell formation induced by Notch signaling. JAK/STAT signaling may also regulate dpp expression in the male GSC niche, suggesting a common origin of female and male GSC niches.

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24

Arai, Fumio. "Hematopoietic stem cells and niche cell populations." Inflammation and Regeneration 32, no. 4 (2012): 152–57. http://dx.doi.org/10.2492/inflammregen.32.152.

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Crittenden, Sarah L., ChangHwan Lee, Ipsita Mohanty, Sindhu Battula, Karla Knobel, and Judith Kimble. "Sexual dimorphism of niche architecture and regulation of the Caenorhabditis elegans germline stem cell pool." Molecular Biology of the Cell 30, no. 14 (July 2019): 1757–69. http://dx.doi.org/10.1091/mbc.e19-03-0164.

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Stem cell maintenance by niche signaling is a common theme across phylogeny. In the Caenorhabditis elegans gonad, the broad outlines of germline stem cell (GSC) regulation are the same for both sexes: GLP-1/Notch signaling from the mesenchymal distal tip cell niche maintains GSCs in the distal gonad of both sexes and does so via two key stem cell regulators, SYGL-1 and LST-1. Yet most recent analyses of niche signaling and GSC regulation have focused on XX hermaphrodites, an essentially female sex making sperm in larvae and oocytes in adults. Here we focus on GSC regulation in XO males. Sexual dimorphism of niche architecture, reported previously, suggested that the molecular responses to niche signaling or numbers of GSCs might also be sexually distinct. Remarkably, this is not the case. This work extends our understanding of the sexually dimorphic niche architecture, but also demonstrates that the dimorphic niches drive a similar molecular response and maintain a similar number of GSCs in their stem cell pools.

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Ehninger, Armin, and Andreas Trumpp. "The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in." Journal of Experimental Medicine 208, no. 3 (March 14, 2011): 421–28. http://dx.doi.org/10.1084/jem.20110132.

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Stem cell niches are defined as the cellular and molecular microenvironments that regulate stem cell function together with stem cell autonomous mechanisms. This includes control of the balance between quiescence, self-renewal, and differentiation, as well as the engagement of specific programs in response to stress. In mammals, the best understood niche is that harboring bone marrow hematopoietic stem cells (HSCs). Recent studies have expanded the number of cell types contributing to the HSC niche. Perivascular mesenchymal stem cells and macrophages now join the previously identified sinusoidal endothelial cells, sympathetic nerve fibers, and cells of the osteoblastic lineage to form similar, but distinct, niches that harbor dormant and self-renewing HSCs during homeostasis and mediate stem cell mobilization in response to granulocyte colony-stimulating factor.

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Yatsenko, Andriy S., and Halyna R. Shcherbata. "Distant activation of Notch signaling induces stem cell niche assembly." PLOS Genetics 17, no. 3 (March 29, 2021): e1009489. http://dx.doi.org/10.1371/journal.pgen.1009489.

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Here we show that multiple modes of Notch signaling activation specify the complexity of spatial cellular interactions necessary for stem cell niche assembly. In particular, we studied the formation of the germline stem cell niche inDrosophilaovaries, which is a two-step process whereby terminal filaments are formed first. Then, terminal filaments signal to the adjacent cap cell precursors, resulting in Notch signaling activation, which is necessary for the lifelong acquisition of stem cell niche cell fate. The genetic data suggest that in order to initiate the process of stem cell niche assembly, Notch signaling is activated among non-equipotent cells via distant induction, where germline Delta is delivered to somatic cells located several diameters away via cellular projections generated by primordial germ cells. At the same time, to ensure the robustness of niche formation, terminal filament cell fate can also be induced by somatic Delta viacis-ortrans-inhibition. This exemplifies a double security mechanism that guarantees that the germline stem cell niche is formed, since it is indispensable for the adjacent germline precursor cells to acquire and maintain stemness necessary for successful reproduction. These findings contribute to our understanding of the formation of stem cell niches in their natural environment, which is important for stem cell biology and regenerative medicine.

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Tsupykov, O. "Neural stem cell niches in the adult mammalian brain." Cell and Organ Transplantology 3, no. 2 (November 30, 2015): 190–94. http://dx.doi.org/10.22494/cot.v3i2.13.

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Stem cells of the central nervous system have received a great deal of attention in neurobiology in the last decade. It has been shown that neurogenesis occurs in the postnatal period in specialized niches of the adult mammalian brain. The niche is a key regulator of stem cell behavior. Recent data underscore the complexity and heterogeneity of the different components of the niche, and the presence of local signaling microdomain. The review is devoted to recent views on the structural organization of neurogenic niches and regulatory factors involved at different stages of neurogenesis in the postnatal period. Understanding of stem cells behavior in the niches can serve as a basis for determination of these cells function in the adult brain.

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Shen, Qin, Yue Wang, Erzsebet Kokovay, Gang Lin, Shu-Mien Chuang, Susan K. Goderie, Badrinath Roysam, and Sally Temple. "Adult SVZ Stem Cells Lie in a Vascular Niche: A Quantitative Analysis of Niche Cell-Cell Interactions." Cell Stem Cell 3, no. 3 (September 2008): 289–300. http://dx.doi.org/10.1016/j.stem.2008.07.026.

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Bardelli, Silvana, and Marco Moccetti. "Remodeling the Human Adult Stem Cell Niche for Regenerative Medicine Applications." Stem Cells International 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/6406025.

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The interactions between stem cells and their surrounding microenvironment are pivotal to determine tissue homeostasis and stem cell renewal or differentiation and regenerationin vivo. Ever since they were postulated in 1978, stem cell niches have been identified and characterized in many germline and adult tissues. Comprehensive studies over the last decades helped to clarify the critical components of stem cell niches that include cellular, extracellular, biochemical, molecular, and physical regulators. This knowledge has direct impact on their inherent regenerative potential. Clinical applications demand readily available cell sources that, under controlled conditions, provide a specific therapeutic function. Thus, translational medicine aims at optimizingin vitroorin vivothe various components and complex architecture of the niche to exploit its therapeutic potential. Accordingly, the objective is to recreate the natural niche microenvironment during cell therapy process development and closely comply with the requests of regulatory authorities. In this paper, we review the most recent advances of translational medicine approaches that target the adult stem cell natural niche microenvironment for regenerative medicine applications.

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Mansour, Anna, Grazia Abou-Ezzi, Ewa Sitnicka, Sten Eirik W. Jacobsen, Abdelilah Wakkach, and Claudine Blin-Wakkach. "Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow." Journal of Experimental Medicine 209, no. 3 (February 20, 2012): 537–49. http://dx.doi.org/10.1084/jem.20110994.

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Formation of the hematopoietic stem cell (HSC) niche in bone marrow (BM) is tightly associated with endochondral ossification, but little is known about the mechanisms involved. We used the oc/oc mouse, a mouse model with impaired endochondral ossification caused by a loss of osteoclast (OCL) activity, to investigate the role of osteoblasts (OBLs) and OCLs in the HSC niche formation. The absence of OCL activity resulted in a defective HSC niche associated with an increased proportion of mesenchymal progenitors but reduced osteoblastic differentiation, leading to impaired HSC homing to the BM. Restoration of OCL activity reversed the defect in HSC niche formation. Our data demonstrate that OBLs are required for establishing HSC niches and that osteoblastic development is induced by OCLs. These findings broaden our knowledge of the HSC niche formation, which is critical for understanding normal and pathological hematopoiesis.

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Congrains, Ada, Juares Bianco, Renata G. Rosa, Rubia I. Mancuso, and Sara T. O. Saad. "3D Scaffolds to Model the Hematopoietic Stem Cell Niche: Applications and Perspectives." Materials 14, no. 3 (January 26, 2021): 569. http://dx.doi.org/10.3390/ma14030569.

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Hematopoietic stem cells (HSC) are responsible for the production of blood and immune cells during life. HSC fate decisions are dependent on signals from specialized microenvironments in the bone marrow, termed niches. The HSC niche is a tridimensional environment that comprises cellular, chemical, and physical elements. Introductorily, we will revise the current knowledge of some relevant elements of the niche. Despite the importance of the niche in HSC function, most experimental approaches to study human HSCs use bidimensional models. Probably, this contributes to the failure in translating many in vitro findings into a clinical setting. Recreating the complexity of the bone marrow microenvironment in vitro would provide a powerful tool to achieve in vitro production of HSCs for transplantation, develop more effective therapies for hematologic malignancies and provide deeper insight into the HSC niche. We previously demonstrated that an optimized decellularization method can preserve with striking detail the ECM architecture of the bone marrow niche and support HSC culture. We will discuss the potential of this decellularized scaffold as HSC niche model. Besides decellularized scaffolds, several other methods have been reported to mimic some characteristics of the HSC niche. In this review, we will examine these models and their applications, advantages, and limitations.

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Wong, Victor W., Benjamin Levi, Jayakumar Rajadas, Michael T. Longaker, and Geoffrey C. Gurtner. "Stem Cell Niches for Skin Regeneration." International Journal of Biomaterials 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/926059.

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Stem cell-based therapies offer tremendous potential for skin regeneration following injury and disease. Functional stem cell units have been described throughout all layers of human skin and the collective physical and chemical microenvironmental cues that enable this regenerative potential are known as the stem cell niche. Stem cells in the hair follicle bulge, interfollicular epidermis, dermal papillae, and perivascular space have been closely investigated as model systems for niche-driven regeneration. These studies suggest that stem cell strategies for skin engineering must consider the intricate molecular and biologic features of these niches. Innovative biomaterial systems that successfully recapitulate these microenvironments will facilitate progenitor cell-mediated skin repair and regeneration.

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Beyazyildiz, Emrullah, Ugur Acar, and Gungor Sobaci. "Animal Models of Dry Eye Syndrome for Stem Cell Based Therapies." Niche Journal 1, no. 3 (January 28, 2014): 49–51. http://dx.doi.org/10.5152/niche.2014.107.

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Guler, Basak, Sevtap Hamdemir Kilic, and Tuncay Delibasi. "A Brief Review: From Spermatogonial Stem Cell to Spermatids in Mammals." Niche Journal 3, no. 2 (February 22, 2016): 24–27. http://dx.doi.org/10.5152/niche.2015.217.

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Gong, Meihua, Pan Zhang, Chunyang Li, Xu Ma, and Daping Yang. "Protective Mechanism of Adipose-Derived Stem Cells in Remodelling of the Skin Stem Cell Niche During Photoaging." Cellular Physiology and Biochemistry 51, no. 5 (2018): 2456–71. http://dx.doi.org/10.1159/000495902.

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Background/Aims: Skin photoaging is primarily caused by the functional attrition of skin stem cells. The skin stem cell niche plays an important role in maintaining stem cell survival and behaviour. In our study, we hypothesized that UVB irradiation induces skin photoaging by changing skin stem cell niches and that transferred adipose-derived stem cells (ADSCs) can remodel the niches by affecting the BMP signalling pathway and transdifferentiating into skin stem cells. Methods: Sixty-four C57BL/6J mice were divided into the following groups: a control group, the UVB group and the UVB+ADSCs group. Western blot assays, immunofluorescence analysis and real-time PCR were used to measure differences in the expression of niche components among the three groups. Furthermore, we tested whether transplanted ADSCs express skin stem cell markers, such as p63, α6-integrin and CD34. Results: The expression levels of Bmp4, its downstream factors Smad1 and MAPK1 and a regulatory factor of the niche, i.e., NFATc1, were lower in the UVB group than were those in the control group (P< 0.05) but higher in the UVB+ADSCs group than were those in the UVB group (P< 0.05). Compared with Bmp4, Nanog (a downstream factor of Bmp4), and MMP13 (a regulatory factor of the niche), ICAM-1 (a proinflammatory gene), p63 (a basal transcription factor), β1-integrin, Mtnr1a and Tyr (melanogenesis-related factors) showed the opposite expression trends (P< 0.05). Bmp2 and Collagen IV levels did not significantly change among the three groups (P> 0.05). Skin stem cell markers, such as p63, α6-integrin and CD34, were coexpressed in the ADSCs, which suggested the ADSCs may transdifferentiate into skin stem cells. Conclusion: We found that UVB irradiation results in typical photoaging signs by altering skin stem cell niches and that Bmp4 was a key factor in BMP signalling in hair follicles. ADSCs reversed these typical photoaging signs by remodelling skin stem cell niches through BMP4 pathway modulation and transdifferentiation into skin stem cells.

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Nie, Daotai. "Cancer stem cell and niche." Frontiers in Bioscience S2, no. 1 (2010): 184–93. http://dx.doi.org/10.2741/s56.

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Andreotti, Julia P., Walison N. Silva, Alinne C. Costa, Caroline C. Picoli, Flávia C. O. Bitencourt, Leda M. C. Coimbra-Campos, Rodrigo R. Resende, et al. "Neural stem cell niche heterogeneity." Seminars in Cell & Developmental Biology 95 (November 2019): 42–53. http://dx.doi.org/10.1016/j.semcdb.2019.01.005.

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Weitzman, Jonathan B. "Characterizing a stem cell niche." Genome Biology 3 (2002): spotlight—20020913–01. http://dx.doi.org/10.1186/gb-spotlight-20020913-01.

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Park, Dongsu. "The hematopoietic stem cell niche." Frontiers in Bioscience 17, no. 1 (2012): 30. http://dx.doi.org/10.2741/3913.

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De Rooij, Dirk G. "The spermatogonial stem cell niche." Microscopy Research and Technique 72, no. 8 (August 2009): 580–85. http://dx.doi.org/10.1002/jemt.20699.

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SHORTT, AJ. "The limbal stem cell niche." Acta Ophthalmologica 91 (August 2013): 0. http://dx.doi.org/10.1111/j.1755-3768.2013.3731.x.

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Lane, Steven W., and Florian H. Heidel. "Hacking the stem cell niche." Blood 129, no. 22 (June 1, 2017): 2951–52. http://dx.doi.org/10.1182/blood-2017-04-777789.

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Frenette, Paul S., Simón Méndez-Ferrer, Daniel Lucas-Alcaraz, Michela Batista, Sergio Lira, Tatyana V. Michurina, and Grigori N. Enikolopov. "The Hematopoietic Stem Cell Niche." Blood 114, no. 22 (November 20, 2009): SCI—49—SCI—49. http://dx.doi.org/10.1182/blood.v114.22.sci-49.sci-49.

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Abstract Abstract SCI-49 The concept of stem cell niche, proposed by Schofield 30 years ago, refers to the ability of the microenvironment to regulate stem cell fate. The niche provides critical signals allowing hematopoietic stem cells (HSC) to survive, and if so, whether to remain in or to leave the niche (mobilization), or whether to remain quiescent or divide. Some of these signals originate locally from the niche cell(s) but others are coming from afar. For example, we have found that signals from the sympathetic nervous system (SNS) promote the release of HSCs from the bone marrow (BM) niche. Under steady-state conditions, HSC egress in blood is orchestrated in a circadian manner where the fluctuations of circulating HSCs/progenitors are matched with antiphase oscillations in the expression of Cxcl12 mRNA in the BM microenvironment. These oscillations are entrained in the brain by the molecular clock through the local delivery of norepinephrine by SNS nerve terminals in the BM, and transmitted specifically by the β3 adrenergic receptor (Adrβ3) expressed on CXCL12-producing stromal cells, thereby leading to the cyclical degradation of the Sp1 transcription factor. In humans, the circadian release of HSC is inverted compared to rodents and may influence the stem cell yield even when mobilization is enforced by granulocyte colony-stimulating factor (G-CSF), suggesting the potential benefit to harvest HSCs in the clinic at the optimal circadian time. Given the coupling of nervous signals with the stem cell niche, we would expect that the stromal cell forming the niche would be intimately associated with nerve fibers. We have recently found using transgenic mice expressing the green fluorescent protein (GFP) under the Nestin promoter elements (Nes-Gfp), that GFP+ cells (referred to as Nestin+) form a HSC niche in the marrow. Nestin+ cells comprise a relatively small subset (0.08 ± 0.01%) of total BM nucleated cells that is anatomically and functionally associated with the vast majority of CD150+ CD48- Lin- HSCs near blood vessels and SNS fibers of the BM. Nestin+ niche cells express high levels of core genes regulating HSC retention (Cxcl12, Kit ligand, Vcam-1, Angiopoietin-1), and these genes are downregulated by mobilization induced by G-CSF or administration of Adrβ3 agonists. We have identified putative Nestin+ niche cells as bona fide mesenchymal stem cells (MSCs) since they can be propagated as single clonal spheres capable of self-renewal, dramatic in vivo expansion, and multipotency to form osteoblasts, adipocytes, and chondocytes. These data argue for a unique bone marrow niche formed by the pairing of the two rare stem cells, mesenchymal and hematopoietic, that exist in the marrow. Co-authors: Simón Méndez-Ferrer, Ph.D., Daniel Lucas, Ph.D., Michela Batista, Ph.D., Sergio A. Lira, M.D., Mount Sinai School of Medicine, New York, NY; Tatyana V. Michurina, Ph.D., Grigori N. Enikolopov Ph.D., Cold Spring Harbor Laboratory, Cold Spring Harbor, NY Disclosures Frenette: Glycomimetic: Research Funding.

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Conover, Joanne C., and Ryan Q. Notti. "The neural stem cell niche." Cell and Tissue Research 331, no. 1 (October 6, 2007): 211–24. http://dx.doi.org/10.1007/s00441-007-0503-6.

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Gómez-Gaviro, Maria Victoria, Robin Lovell-Badge, Francisco Fernández-Avilés, and Enrique Lara-Pezzi. "The Vascular Stem Cell Niche." Journal of Cardiovascular Translational Research 5, no. 5 (May 30, 2012): 618–30. http://dx.doi.org/10.1007/s12265-012-9371-x.

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Koch, Ute, and Freddy Radtke. "Haematopoietic stem cell niche inDrosophila." BioEssays 29, no. 8 (2007): 713–16. http://dx.doi.org/10.1002/bies.20613.

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Abdul-Al, Mohamed, George Kumi Kyeremeh, Morvarid Saeinasab, Saeed Heidari Keshel, and Farshid Sefat. "Stem Cell Niche Microenvironment: Review." Bioengineering 8, no. 8 (July 28, 2021): 108. http://dx.doi.org/10.3390/bioengineering8080108.

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The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live at the bottom of the limbal crypts, in a physically enclosed microenvironment with a number of neighboring niche cells. Scientists also simplified features of these diverse microenvironments for more analysis in situ by designing and recreating features of different SCNs. Recent methods for regenerating the corneal epithelium after serious trauma, including burns and allergic assaults, focus mainly on regenerating the LESCs. Mesenchymal stem cells, which can transform into self-renewing and skeletal tissues, hold immense interest for tissue engineering and innovative medicinal exploration. This review summarizes all types of LESCs, identity and location of the human epithelial stem cells (HESCs), reconstruction of LSCN and artificial stem cells for self-renewal.

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Donnelly, Hannah, Manuel Salmeron-Sanchez, and Matthew J. Dalby. "Designing stem cell niches for differentiation and self-renewal." Journal of The Royal Society Interface 15, no. 145 (August 2018): 20180388. http://dx.doi.org/10.1098/rsif.2018.0388.

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Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche . Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro . In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries.

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Olson, Timothy S., Satoru Otsuru, Ted J. Hofmann, Massimo Dominici, and Edwin M. Horwitz. "Expansion of the Endosteal Hematopoietic Stem Cell Niche Following Myeloablative and Reduced Intensity Conditioning Is Triggered By Hematopoietic Cell Loss." Blood 124, no. 21 (December 6, 2014): 1090. http://dx.doi.org/10.1182/blood.v124.21.1090.1090.

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Abstract The efficiency and durability of donor hematopoietic stem cell (HSC) engraftment at specialized niches within recipient bone marrow (BM) are critical determinants of successful clinical stem cell transplant (SCT). Osteolineage elements of BM niches play active, critical roles in regulating HSC engraftment, differentiation, and self-renewal both during homeostasis and post-SCT. We have previously shown that SCT preparative regimens consisting of myeloablative total body irradiation (MB-TBI) result in expansion of osteolineage niche cells at the endosteal surface of metaphyseal bone. This expansion is facilitated by IGF-1 and megakaryocyte-derived PDGF-BB signaling, and is required for optimal HSC engraftment. However, the pathway that integrates these signals to induce expansion remains undefined, and whether expansion is unique to conditioning with MB-TBI due to direct effects on osteolineage cells is also not known. We now present data using chemotherapy-based and reduced intensity conditioning (RIC) models, demonstrating that niche expansion is triggered by hematopoietic cell loss, and not by direct effects of conditioning agents on the niche. In vitro, MB-TBI (1125 cGy) inhibited primary murine osteoblast (OB) growth and increased apoptosis (Annexin V+ OB at 72 hours: TBI 17% versus control 4%, p < 0.001). In contrast, busulfan treatment caused significantly less OB growth inhibition versus MB-TBI, with no increased apoptosis compared to sham-treated controls. We therefore conditioned wildtype (WT) C57BL/6 mice with myeloablative busulfan (Day -7 to -4) and cyclophosphamide (Day -3 to -2) (BuCy) in a schedule similar to clinical SCT regimens. Endosteal niche expansion increased over this time course, correlating with the extent of hematopoietic ablation, with most expansion occurring prior to cyclophosphamide administration. Maximal expansion occurred by the end of the treatment course, and based on a quantitative scoring index, was not significantly different than maximal MB-TBI-induced niche expansion, demonstrating that niche expansion is not specific to radiation-based conditioning. As with MB-TBI treatment, BuCy-treated recipients of GFP+donor BM consistently exhibited >95% donor chimerism. We next investigated whether RIC regimens can mediate niche expansion, using an anti-cKit antibody (clone ACK2) known to enable donor engraftment when administered alone in immunodeficient mice or in combination with low dose irradiation (LD-TBI, 300 cGy) in WT mice. ACK2 treatment alone resulted in modest endosteal cell expansion (33% of MB-TBI induced expansion), correlating with transient reductions in host BM cellularity, but absence of definitive donor engraftment in ACK2-treated WT mice. In contrast, LD-TBI alone or in combination with ACK2 produced 58% and 74%, respectively, of the endosteal expansion seen following MB-TBI. Interestingly, while these regimens reduced total BM cellularity by 85% (LD-TBI) and 93% (LD-TBI + ACK2), and led to clearance of BM Lin-Sca1+cKit+(LSK) progenitors, this lack of full niche expansion correlated with incomplete and inconsistent donor chimerism in SCT recipients. Finally, to prove that endosteal niche expansion results from signals triggered specifically by hematopoietic cell loss, we crossed mice expressing Cre-recombinase under control of the CD45 promoter (CD45Cre) with mice expressing inducible diphtheria toxin receptor (iDTRlox). When treated with diphtheria toxin (DT), BM cellularity in these mice was reduced by 90%, and this targeted ablation of hematopoietic cells was sufficient to induce similar expansion of endosteal mesenchymal cells as seen with radiation or chemotherapy-based conditioning regimens. Taken together, our results demonstrate that endosteal niche expansion occurs in response to both radiation- and chemotherapy-based SCT conditioning, and that the degree of expansion correlates with both conditioning intensity and with the subsequent degree of donor cell engraftment/chimerism in SCT recipients. Importantly, expansion is triggered not by direct effects of the preparative regimen on mesenchymal niche cells, but rather by loss of hematopoietic cells. These findings provide important insights into how SCT conditioning modulates niche function, and suggests that therapeutic strategies to enhance niche function may be effective in improving engraftment outcomes following RIC SCT. Disclosures No relevant conflicts of interest to declare.

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