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Human Bone Marrow Mesenchymal Stem Cells: A Systematic Reappraisal Via the Genostem Experience

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Abstract

Genostem (acronym for “Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to the bed side”) has been an European consortium of 30 teams working together on human bone marrow Mesenchymal Stem Cell (MSC) biological properties and repair capacity. Part of Genostem activity has been dedicated to the study of basic issues on undifferentiated MSCs properties and on signalling pathways leading to the differentiation into 3 of the connective tissue lineages, osteoblastic, chondrocytic and tenocytic. We have evidenced that native bone marrow MSCs and stromal cells, forming the niche of hematopoietic stem cells, were the same cellular entity located abluminally from marrow sinus endothelial cells. We have also shown that culture-amplified, clonogenic and highly-proliferative MSCs were bona fide stem cells, sharing with other stem cell types the major attributes of self-renewal and of multipotential priming to the lineages to which they can differentiate (osteoblasts, chondrocytes, adipocytes and vascular smooth muscle cells/pericytes). Extensive transcription profiling and in vitro and in vivo assays were applied to identify genes involved in differentiation. Thus we have described novel factors implicated in osteogenesis (FHL2, ITGA5, Fgf18), chondrogenesis (FOXO1A) and tenogenesis (Smad8). Another part of Genostem activity has been devoted to studies of the repair capacity of MSCs in animal models, a prerequisite for future clinical trials. We have developed novel scaffolds (chitosan, pharmacologically active microcarriers) useful for the repair of both bone and cartilage. Finally and most importantly, we have shown that locally implanted MSCs effectively repair bone, cartilage and tendon.

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Aknowledgments

Work supported by the European Community (Key action 1.2.4-3 Integrated Project Genostem, contract N° 503161).

Author information

Authors and Affiliations

  1. Institut National de la Santé et Recherche Médicale (INSERM) U972, Hôpital de Bicêtre, Le Kremlin Bicêtre, France

    Pierre Charbord

  2. Faculty of Medicine, Technion - Israel institute of Technology, Haifa, Israel

    Erella Livne

  3. Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany

    Gerhard Gross

  4. Department of Rheumatology and Clinical Immunology, Laboratory for tissue engineering, Charité-University Medicine, Berlin, Germany

    Thomas Häupl

  5. University of Minho, Headquarters of the European Institute of Excellence in Tissue Engineering and Regenerative Medicine, Dept Polymer Engn, 3Bs Research Group Biomaterials, Biodegradables & Biomimetics, and PT Government Associated Laboratory, Institute of Biotechnology & Bioengineering, IBB, Guimaraes, Portugal

    Nuno M. Neves

  6. Institut National de la Recherche et Santé Médicale (INSERM) U606, University Paris Diderot, Paris, France

    Pierre Marie

  7. Department of Experimental Medicine, University La Sapienza and Biomedical Science Park San Raffaele, Rome, Italy

    Paolo Bianco

  8. Institut National de la Recherche et Santé Médicale (INSERM) U844, Hôpital Saint Eloi-INM, Montpellier, France

    Christian Jorgensen

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  1. Pierre Charbord
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Correspondence to Pierre Charbord.

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Charbord, P., Livne, E., Gross, G. et al. Human Bone Marrow Mesenchymal Stem Cells: A Systematic Reappraisal Via the Genostem Experience. Stem Cell Rev and Rep 7, 32–42 (2011). https://doi.org/10.1007/s12015-010-9125-6

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  • DOI: https://doi.org/10.1007/s12015-010-9125-6

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