Simulated microgravity affects stroma-dependent ex vivo myelopoiesis

Area of Science:

• Space biology
• Hematology
• Cell biology

Background:

• Microgravity negatively impacts human physiology, including hematopoiesis.
• The bone marrow niche's hematopoietic stem and progenitor cells (HSPCs) and stromal cells relationship is crucial for blood formation.

Purpose of the Study:

• To compare the efficacy of ex vivo expansion of HSPCs with native or osteocommitted mesenchymal stem cells (MSCs) under simulated microgravity (Smg).
• To investigate the impact of Smg on HSPC populations and their interaction with MSCs.

Main Methods:

• Hematopoietic stem and progenitor cells (HSPCs) co-cultured with native or osteocommitted MSCs were exposed to simulated microgravity (Smg) using a Random Positioning Machine (RPM).
• Flow cytometry was used to analyze HSPC populations (CD34, CD133).
• Colony-forming unit (CFU) assays assessed hematopoietic progenitor numbers.
• Cytokine levels (VEGF, eotaxin, GRO-a, RANTES, IL-6, IL-8, IL-13, G-CSF, MCP-3, MIP-1b) were measured.

Main Results:

• Smg exposure decreased MSC-associated HSPCs and increased floating HSPCs, with a higher proportion of late CD34+/133- progenitors.
• Total CFUs, including erythroid (BFU-E) and granulocytic (CFU-G), were reduced under Smg.
• Osteo-MSCs supported late primitive CD34+ and committed HSPCs, increasing CFUs and CD235a+ erythroid progenitors, but this support was diminished under Smg.
• Smg altered cytokine profiles, increasing VEGF, eotaxin, and GRO-a, while decreasing RANTES in co-cultures. Specific cytokines increased in osteo-MSC vs. intact MSC co-cultures.

Conclusions:

• Simulated microgravity leads to a misbalance between primitive and committed HSPCs.
• Osteocommitted MSCs exhibit decreased hematopoiesis-supportive activity under Smg.
• These changes likely contribute to hematopoietic disorders observed during space flights.