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Microgravity Alters the In Vivo Differentiative Potential of Mesenchymal Stem Cells (MSC).   A.M. Frias1,2, J. Chamberlain1, S. Mazhari, C.Porada1, E.D. Zanjani1, J.M.S. Cabral2, G.Almeida‑Porada1. 1Dept Animal Biotech, UNR, USA and 2CEBQ, IST, Portugal

   We and others have shown that MSC are able upon transplantation to differentiate into specialized cells of multiple organs. Thus we hypothesized that MSC may be responsible, in part, for maintaining   normal replacement of cells within different organs. In these studies, we investigated whether microgravity (mG) altered the differentiative potential of MSCs in such a way as to hinder the ability of MSC to differentiate into other cells/lineages. To this end bone marrow-derived MSC (BMMSC), fetal liver MSC (FLMSC), or brain MSC (BRMSC) were seeded onto cytodex-3 beads and grown in a rotary cell culture system for 5 days, and subsequently transplanted at a concentration of 1 million cells/fetus into 12 fetal-sheep recipients. Flow cytometric evaluation of the recipients at 60 days post-transplant for the presence of donor-derived blood and BM showed that all MSC populations generated multilineage hematopoietic cells, including CD34+ cells, at differing levels. However, when the levels of human cell engraftment of these animals were compared with animals transplanted with the MSCs grown in normal G cultures, it became apparent that MSCs grown under mG conditions generated multilineage blood cells at a lower level than their regular culture counterpart, suggesting that mG impairs either MSCs engraftment and/or in vivo differentiation.  Other organs such as liver and pancreas were also evaluated for the presence of human organ-specific cells. We found that differentiation towards a hepatocyte-like phenotype was impaired in MSCs grown under mG conditions, while differentiation towards a pancreatic phenotype was highly enhanced. Most of the sheep transplanted with MSC grown under microgravity conditions contained human b-cells producing of human insulin. These studies suggest that stem cells are affected by mG and that this may impact upon the health of humans subjected to conditions of mG during space travel. (Supported by NASA NAG9-1340)