Molecular and Morphological Features of Mesenchymal Stem Cells Under Microgravity

Pala, Renzo

Mesenchymal stem cells (MSCs) are multipotent progenitors with high potential for regenerative medicine, due to their self-renewal, multilineage differentiation, and immunomodulatory properties. Among them, Wharton’s Jelly-derived MSCs (WJ-MSCs) represent a promising resource, as they display youthful phenotypes, reduced ethical concerns, and a high degree of plasticity. However, environmental factors such as microgravity—experienced during spaceflight or simulated on Earth—profoundly affect cellular physiology, raising questions about their impact on stemness, senescence, and regenerative potential. This study investigated the molecular and morphological responses of WJ-MSCs exposed to simulated microgravity using a 3D random positioning machine. Gene expression analysis was performed on key regulators of pluripotency (OCT-4, SOX2, NANOG), senescence (p16, p19, p21, p53), apoptosis (BAX, Bcl-2, cytochrome c), oxidative stress (SIRT1, NOX4, HSP60, HSP70), and cytoskeletal organization (β-actin, β-tubulin). Results showed that short-term microgravity exposure initially enhanced stemness and stress-response gene expression, while prolonged exposure induced a progressive downregulation of pluripotency markers, activation of senescence pathways, oxidative imbalance, and cytoskeletal disorganization. These alterations compromised cell survival and differentiation potential, highlighting the sensitivity of WJ-MSCs to gravitational changes. The findings provide new insights into how microgravity shapes stem cell biology, with implications for regenerative medicine, tissue engineering, and long-term human space exploration. Understanding these adaptive and maladaptive responses may aid in developing countermeasures to protect stem cell functionality in altered gravitational environments, supporting both clinical applications on Earth and biomedical strategies for future space missions.

Mesenchymal stem cells (MSCs) are multipotent progenitors with high potential for regenerative medicine, due to their self-renewal, multilineage differentiation, and immunomodulatory properties. Among them, Wharton’s Jelly-derived MSCs (WJ-MSCs) represent a promising resource, as they display youthful phenotypes, reduced ethical concerns, and a high degree of plasticity. However, environmental factors such as microgravity—experienced during spaceflight or simulated on Earth—profoundly affect cellular physiology, raising questions about their impact on stemness, senescence, and regenerative potential. This study investigated the molecular and morphological responses of WJ-MSCs exposed to simulated microgravity using a 3D random positioning machine. Gene expression analysis was performed on key regulators of pluripotency (OCT-4, SOX2, NANOG), senescence (p16, p19, p21, p53), apoptosis (BAX, Bcl-2, cytochrome c), oxidative stress (SIRT1, NOX4, HSP60, HSP70), and cytoskeletal organization (β-actin, β-tubulin). Results showed that short-term microgravity exposure initially enhanced stemness and stress-response gene expression, while prolonged exposure induced a progressive downregulation of pluripotency markers, activation of senescence pathways, oxidative imbalance, and cytoskeletal disorganization. These alterations compromised cell survival and differentiation potential, highlighting the sensitivity of WJ-MSCs to gravitational changes. The findings provide new insights into how microgravity shapes stem cell biology, with implications for regenerative medicine, tissue engineering, and long-term human space exploration. Understanding these adaptive and maladaptive responses may aid in developing countermeasures to protect stem cell functionality in altered gravitational environments, supporting both clinical applications on Earth and biomedical strategies for future space missions