Preconditioning with StemRegenin 1 enhances human adipose stromal/stem cells proliferation, migration, and protection...

Adipose-derived stromal/stem cells (ASCs) are promising for the treatment of many diseases, including tissue injury or degeneration associated with serious disease and high morbidity. The extent of cell therapy effectiveness, however, may be limited by the lower survival of implanted cells in environments of tissue damage. Therefore, strategies to improve cell survival are important, such as by pretreating/preconditioning cells with a beneficial agent. We investigated the pretreatment of human ASCs (hASCs) with StemRegenin 1 (SR1), a purine derivative used in clinical protocols for in vitro hematopoietic stem/progenitor cell expansion. We pretreated hASCs with SR1 and analyzed the resulting cells (SR1-hASCs) as compared to non-treated cells (NT-hASCs). We noted that treatment with SR1 significantly increased the proliferation and migration of hASCs, as well as their secretion of paracrine factors of interest, and did not affect their cell differentiation capacity. Furthermore, when these SR1-hASCs were subsequently exposed to antimycin A, a mitochondrial respiratory chain inhibitor, they showed significantly higher antioxidative, anti-apoptotic, and pro-survival abilities as compared to NT-hASCs. Since oxidative stress and other harsh environments result from tissue damage, our results support that the preconditioning of hASCs with SR1 may enhance their protective, reparative, and regenerative, and thus therapeutic, efficacy.