Bone marrow-derived mesenchymal stem cells (BM-MSCs) play a role in wound healing and tissue repair and may also be useful for organ regeneration. As we have demonstrated previously that A 2A adenosine receptors (A 2A R) promote tissue repair and wound healing by stimulating local repair mechanisms and enhancing accumulation of endothelial progenitor cells, we investigated whether A 2A R activation modulates BM-MSC proliferation and differentiation. BM-MSCs were isolated and cultured from A 2A -deficient and ecto-5′nucleotidase (CD73)-deficient female mice; the MSCs were identified and quantified by a CFU-fibroblast (CFU-F) assay. Procollagen α2 type I expression was determined by Western blotting and immunocytochemistry. MSC-specific markers were examined in primary cells and third-passage cells by cytofluorography. PCR and real time-PCR were used to quantitate adenosine receptor and CD73 expression. There were significantly fewer CFU-Fs in cultures of BM-MSCs from A 2A R knockout (KO) mice or BM-MSCs treated with the A 2A R antagonist ZM241385, 1 μM. Similarly, there were significantly fewer procollagen α2 type I-positive MSCs in cultures from A 2A R KO and antagonist-treated cultures as well. In late passage cells, there were significantly fewer MSCs from A 2A KO mice expressing CD90, CD105, and procollagen type I ( P <0.05 for all; n =3). These findings indicate that adenosine and adenosine A 2A R play a critical role in promoting the proliferation and differentiation of mouse BM-MSCs.
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Adenosine A2A receptors play an active role in mouse bone marrow-derived mesenchymal stem cell development
Katebi, Majid; Soleimani, Mansooreh; Cronstein, Bruce N.
Follow Journal of Leukocyte Biology
, Volume 85 (3): 438
Fed of American Socs for Experimental Biology – Mar 1, 2009
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