Deciphering the role of the bone marrow microenvironment on wound healing


Mechanobiological and physiological consequences of long-duration spaceflight are of increasing concern for human space exploration. Our work, and that of others, has demonstrated that spaceflight factors significantly impair somatic stem cell-based tissue regeneration, leading to degenerative decline in highly regenerative tissues (e.g., skin and musculoskeletal systems) that is similar to degeneration that occurs during aging. The BM contains both hematopoietic and mesenchymal lineages and both stem cell populations have a high degree of plasticity and are capable of regenerating functional tissues. Notably, the BM contains precursor cells for the musculoskeletal and immune systems, both of which are significantly affected by spaceflight. Our studies have demonstrated that spaceflight significantly affects bone microstructural properties and that long-duration spaceflight leads to development of an osteoarthritic-like phenotype in both male and female mice 

Spaceflight exposure, including both environmental conditions on the ISS and exposure to microgravity/space radiation, also affects skin health and leads to increased incidence of skin impairments and diseases. Specifically, skin sensitivity, thinning, peeling, dryness and delayed wound healing have been documented in rodents and astronauts, and diseases including psoriasis, dermatitis and folliculitis flare up during spaceflight exposure. Several studies have also documented that prolonged exposure to the spaceflight environment results in accelerated aging of the skin, causing loss of thickness and elasticity in both rodents and astronauts. 

Therefore in this project we aim to comprehensively elucidate cellular and molecular mechanisms underpinning the deleterious impact of spaceflight-induced mitochondrial dysfunction and senescence on stem cell-based tissue regeneration in two highly regenerative and inter-connected tissues - skin and bone. We are using innovative, inducible rodent models and a potent, dietary antioxidant, shown to be safe in humans, to identify novel countermeasures that may preserve tissue health in long-duration space exploration.

Funding Agency