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Effects of Severe Hypoxia on Bone Marrow Mesenchymal Stem Cells Differentiation Potential

DOI: 10.1155/2013/232896

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Abstract:

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions. Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS). Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiation capacity in severe hypoxic cultures. Conclusions. In our experimental conditions, severe hypoxia affects the in vitro differentiation potential of BM-MSCs. Adipogenic, osteogenic, and chondrogenic differentiations are absent in severe hypoxic conditions. Our work underlines that severe hypoxia slows cell differentiation by means of molecular mechanisms since a decrease in the expression of adipocyte-, osteoblast-, and chondrocyte-specific genes was observed. 1. Introduction Mesenchymal stem cells (MSCs) are multipotent cells that can be expanded ex vivo and induced, either in vitro or in vivo, to terminally differentiate into multiple lineages [1–5]. These cells are located in bone marrow (BM), around blood vessels, in fat, skin, muscle, and other tissues, and their presence contributes to the reparative capacity of these tissues. MSCs from different tissue sources can have biologic distinctions. In this way, MSCs derived from bone marrow show a higher potential for osteogenic differentiation [6], while MSCs of synovial origin show a greater tendency toward chondrogenic differentiation [7]. Moreover, under identical culture conditions of differentiation, MSCs isolated from the synovial membrane show more chondrogenic potential than those derived from bone marrow, periosteum, skeletal muscle, or adipose tissue [8]. The recent use of autologous or allogenic stem cells has been suggested as an alternative therapeutic approach for treatment of cartilage defects [9], with these cells representing a promising resource for different tissue engineering and cell-based therapies

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