This study examined how microgravity affects stem cell health and regenerative capacity using human mesenchymal stem cells cultured in simulated microgravity conditions. These findings have important implications for astronaut health and suggest the need for countermeasures to maintain stem cell function during spaceflight. We found that microgravity alters stem cell morphology, proliferation, and differentiation potential. Understanding how spaceflight affects stem cell function is important for maintaining astronaut health during long-duration missions. Results Simulated microgravity altered stem cell morphology, with cells becoming more rounded and less adherent.