Simulated microgravity affects stroma-dependent ex vivo myelopoiesis

Abstract

Microgravity is known negatively affect physiology of living beings, including hematopoiesis. Dysregulation of hematopoietic cells and supporting stroma relationships in bone marrow niche may be in charge. We compared the efficacy of ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) in presence of native or osteocommitted MSCs under simulated microgravity (Smg) using Random Positioning Machine (RPM). In comparison with 1 g, a decrease of MSC-associated HSPCs and an increase of floating HSPCs was observed after 7 days of Smg exposure. Among floating HSPCs, primitive progenitors were presented by late CD34+/133–. Total CFUs as well as erythroid (BFU-E) and granulocytic (CFU-G) numbers were lower. MSC-associated primitive HSPCs demonstrated increased proportion of late CD34+/133- in expense of early CD34-/133+. Osteo-MSCs preferentially supported late primitive CD34+ and more committed HSPCs as followed from increase of CFUs, and CD235a+ erythroid progenitors. Under Smg, an increased VEGF, eotaxin, and GRO-a levels, and a decrease in RANTES were found in the osteo-MSC-HSPC co-cultures. IL-6,-8, -13, G-CSF, GRO-a, MCP-3, MIP-1b, VEGF increased in co-culture with osteo-MSCs vs intact MSCs. Based on the findings, the misbalance between primitive/committed HSPCs and a decrease in hematopoiesis-supportive activity of osteocommitted cells are supposed to underline hematopoietic disorders during space flights.