| FGF-2 Maintains a Niche-Dependent Population of Self-Renewing Highly Potent Non-Adherent Mesenchymal Progenitors Through FGFR2c. | |
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MedLine Citation:
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PMID: 22495904 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Bone marrow mesenchymal stem/stromal cells (MSC) are a heterogeneous population of multipotent progenitors currently under investigation for a variety of applications in regenerative medicine. While self-renewal of stem cells in different tissues has been demonstrated to be regulated by specialized microenvironments called niches, it is still unclear whether a self-renewing niche also exists for MSC. Here we show that primary human bone marrow cultures contain a population of intrinsically non-adherent mesenchymal progenitors (NAMP) with features of more primitive progenitors than the initially adhering Colony Forming Units-fibroblast (CFU-f). In fact, NAMP could generate an adherent progeny: 1) enriched with early mesenchymal populations (CD146+, SSEA-1+ and SSEA-4+); 2) with significantly greater proliferation and multilineage differentiation potential in vitro; and 3) capable of 3-fold greater bone formation in vivo than the corresponding CFU-f. Upon serial replating, NAMP were able to regenerate and expand in suspension as non-adherent clonogenic progenitors, while also giving rise to an adherent progeny. This took place at the cost of a gradual loss of proliferative potential, shown by a reduction in colony size, which could be completely prevented when NAMP were expanded on the initially adhering bone marrow fraction. Mechanistically, we found that NAMP crucially depend on FGF-2 signaling through FGFR2c for their survival and expansion. Further, NAMP maintenance depends at least in part on humoral signals distinct from FGF-2. In conclusion, our data show a niche/progenitor organization in vitro, in which the bone marrow adherent fraction provides a self-renewing microenviroment for primitive non-adherent mesenchymal progenitors. |
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Authors:
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Nunzia Di Maggio; Arne Mehrkens; Adam Papadimitropoulos; Stefan Schaeren; Michael Heberer; Andrea Banfi; Ivan Martin |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-11 |
Journal Detail:
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Title: Stem cells (Dayton, Ohio) Volume: - ISSN: 1549-4918 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9304532 Medline TA: Stem Cells Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 AlphaMed Press. |
Affiliation:
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Departments of Surgery and of Biomedicine, Basel University Hospital, CH 4031 Basel, Switzerland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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