Effect of spaceflight on human stem cell hematopoiesis: suppression of erythropoiesis and myelopoiesis

Abstract

Humans subjected to periods of microgravity develop anemia, thrombocytopenia, and abnormalities in red blood cell structure. The causes of these abnormalities are complex and unclear. The in vitro effects of spaceflight on hematopoietic cell proliferation and differentiation were investigated during the space shuttle missions STS-63 (Discovery) and STS-69 (Endeavour). CD34+ bone marrow progenitor cells were cultured in liquid suspension culture and on hematopoietic supportive stromal cells using hollow-fiber culture modules. One set of cultures was maintained at microgravity (flight cultures) for the last 8-10 days of culture and a second control was at full gravity (ground control). Over the 11- to 13-test-day period, ground control culture total cell number increased 41.0- to 65.5-fold but flight culture total cell number increased only 10.1- to 17.6-fold (57-84% decrease). Comparing ground control cultures and microgravity cultures, respectively, for progenitor cell content, myeloid progenitor cell numbers expanded 2.6- to 17.5-fold compared with 0.9- to 7.0-fold and erythroid progenitor cell numbers expanded 2.0- to 4.1-fold in ground control cultures but actually declined at microgravity (>83% reduction). Moreover, microgravity cultures demonstrated accelerated maturation/differentiation toward the macrophage lineage. These data indicate that spaceflight has a direct effect on hematopoietic progenitor cell proliferation and differentiation and that specific aspects of in vitro hematopoiesis, particularly erythropoiesis, involve gravity-sensitive components.

Microgravity, Stem Cells, and Embryonic Development: Challenges and Opportunities for 3D Tissue Generation

“…For instance, the proliferation of CD34+ was reduced during LEO flights compared to ground controls, with the differentiation toward the macrophage at the expense of human myeloid and erythroid pre-cursors (Davis et al, 1996). On the other hand, despite similarly reduced proliferation during a comparable time span, SMG (RWV) was reported to steer human CD34+ cells toward the myeloid fate, an effect associated with slowed S-phase of the cell cycle (Plett et al, 2004).…”

Simulated microgravity induce apoptosis and down-regulation of erythropoietin receptor of UT-7/EPO cells

“…Both spaceflight (Davis et al, 1996) and modeled experiments (Plett et al, 2004) displaying a direct effect of microgravity on hematopoietic progenitor cell proliferation and differentiation, indicate that there should be an EPO independent mechanism. Moreover, a decrease in responsiveness of the erythropoietic system and erythroid cells to EPO was found in both spaceflight (Allebban et al, 1996) and simulated experiments on the ground (Sytkowski and Davis, 2001), but the mechanisms are still not clear.…”

Stem Cell Health and Tissue Regeneration in Microgravity

“…Additionally, shifts in immune cell phenotypes were noted in experiments fl own on board STS -108 with an increase in the numbers of bone marrow -derived T cells and a decrease in bone marrowderived B cells [44]. Studies on STS -63 and STS -69 with CD34 + bone marrow progenitor cells revealed decreases in total cell number in microgravity samples, and additionally decreased erythropoiesis and increased macrophage differentiation [45]. Furthermore, studies investigating the bone marrow stem cell population in the femoral head of space -fl own mice revealed an accumulation of red blood cells, decreased numbers of megakaryocytes, and decreased capacity of both mesenchymal and hematopoietic stem cells to differentiate into terminal lineages [43].…”