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The Effects of Stimulated Microgravity on Hematopoietic Stem Cell Differentiation into Dendritic Cells.   E. Low 1, Yamagami T1, C.Porada1, G.Almeida‑Porada1   1Dept Animal Biotech, University of Nevada Reno, USA

  It is unknown whether the immune system of individuals involved in space travel retains the integrity that is required to protect against infection. We hypothesize that microgravity (µG) alters the development and/or functionality of critical regulators of the immune system, leading to many of the changes that have been observed in astronauts’ immunity. The generation of an effective immune response requires that antigens be processed and presented to T lymphocytes by antigen presenting cells (APCs), the most potent of which are Dendritic cells (DCs). These cells also function as effector cells in innate immunity against microbes. The aim of this study was to develop a µG culture system to examine the effects of microgravity on the differentiation of human hematopoietic stem cells (HSC) into functional DCs. To this end, adult human bone marrow CD34+ cells were cultured in normal G conditions or in µG conditions either in serum-free media or IMDM /15%FBS with IL-4, GM-CSF, SCF, Flt-3, and TNF-a. Cultured cells were analyzed from day 3-20 for the presence of DC differentiation based on morphology, and expression of HLA-DR, CD123 and/or CD11c by FACS. The serum-free culture system seemed to be optimal for the differentiation of HSC into dendritic cells.  In µG, the RCCS’ rpm influenced the survival of HSC in culture, with 7 rpm being optimal to maintain viability. Although both culture conditions produced higher numbers of myeloid vs. plasmacytoid DCs, CD34+ cells cultured in normal G differentiated into DCs in significantly higher numbers (8-fold) than those cultured under µG.  Maximal differentiation into DCs in normal G occurred at day 10, while in µG it was delayed until day 14.  Thus, our results suggest that µG delays the production DC and reduces the number of these important APC that are generated, providing a possible explanation for some of the alterations in immunity that have been observed in astronauts during space travel.

 (Supported by NASA NAG9-1340)