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mesenchymal stem cells

mesenchymal stem cells - ii29 REPORT Mesenchymal stem cells...

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REPORT Mesenchymal stem cells. A potential source for skeletal repair W E Fibbe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ann Rheum Dis 2002; 61 (Suppl II):ii29–ii31 T he bone marrow serves as a reservoir for different classes of stem cells. In addtion to haematopoietic stem cells the bone marrow comprises a population of marrow stromal cells or mesenchymal stem cells (MSCs). Stromal cells exhibit multilin- eage differentiation capacity, and are able to generate progeni- tors with restricted developmental potential, including fibro- blasts, osteoblasts, adipocytes, and chondrocyte progenitors. 1–3 Recently, techniques have become available to isolate and grow mesenchymal progenitors and to manipulate their growth under defined in vitro culture conditions. As a result MSCs can be rapidly expanded to numbers that are required for clinical application. Here the role of MSCs for repair of bone and cartilage is discussed. MARROW STROMAL CELLS Marrow stromal cells comprise a heterogenous population of cells, including reticular endothelial cells, fibroblasts, adi- pocytes, and osteogenic precursor cells that provide growth fac- tors, cell to cell interactions, and matrix proteins that play a part in the regulation of haematopoiesis. 4–6 The notion that a stromal microenvironment could support haematopoiesis followed by the development of the long term bone marrow culture by Dex- ter. In this system an adherent bone marrow derived stromal culture could support the production of haematopoietic progenitor cells over a period of several weeks to months. Friedenstein 7 already described a population of adherent cells from the bone marrow that were non-phagocytic and exhibited a fibroblast-like appearance. Upon culture at low density either as whole bone marrow or after separation over a density gradient the cells formed characteristic colonies derived from a single precursor, referred to as colony forming unit fibroblastic or CFU-F. After ectopic transplantation under the kidney capsule these cells gave rise to a broad spectrum of differenti- ated connective tissues including bone, cartilage, adipose tissue, and myelosupportive stroma. 7 8 Based on these observations it was proposed that these tissues were derived from a common precursor cell residing in the bone marrow, termed the stromal stem cell, the bone marrow stromal stem cell, the mesenchymal stem cell, or the skeletal stem cell. 9 10 MSCs are present in post-natal bone marrow and also in the bone marrow of adults and there is evidence that the frequency declines with age. 1 For instance the frequency in the newborn is about 1/10, 4 which decreases to about 1/2 × 10 6 in an 80 years old person. After allogeneic stem cell transplantation the frequency of CFU-F is transiently reduced in children and recovers over a period of several years, while the defect is per- manent in adult recipients of stem cell grafts. 11 These observa- tions formed the basis for the clinical application of culture expanded MSCs in the context of allogeneic stem cell transplantation.
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