MiR-145-5p Overexpression Improves Stem Cell Transplantation
It is now commonplace for patients to undergo first generation stem cell therapy where the transplanted cells (which may or may not actually be stem cells) are derived from fat tissue. These therapies clearly produce some degree of benefit, primarily suppression of inflammation. There is a high degree of variability of outcomes between patients and from clinic to clinic, however, even when clinicians are following the same protocol. This may be due to the degree of cellular senescence that emerges in transplanted cells, but this is still a topic under investigation. Regardless, various different approaches have been assessed in order to improve the ability of transplanted cells to produce benefits in patients. The research noted here is one example of many.
Adipose-derived stem cells (ADSCs) have been widely applied in translational and regenerative medicine. However, during aging, there is a recognized functional decline in ADSCs, which compromises their therapeutic effectiveness. Currently, the mechanisms of aging-induced stem cell dysfunction remain unclear. Hence, there is a need to elucidate these mechanisms and propose strategies for reversing this functional impairment.
In this study, we found that ADSCs isolated from old donors (O-ADSCs) presented inferior phenotypes and decreased miR-145-5p levels compared to those from young donors (Y-ADSCs). To interrogate the role of miR-145-5p in ADSCs, gain- and loss-of-function approaches were performed. The results indicated that miR-145-5p overexpression in O-ADSCs promoted cellular proliferation and migration, while reducing cell senescence. Further study demonstrated that miR-145-5p could regulate ADSCs function by targeting bone morphogenetic protein binding endothelial cell precursor-derived regulator (BMPER), which is a crucial modulator in angiogenesis. Moreover, in vivo experiments showed that miR-145-5p-overexpressing O-ADSCs accelerated wound healing by promoting wound re-epithelialization and angiogenesis.
Collectively, this study indicates that miR-145-5p works as a positive regulator for optimizing O-ADSCs function, and may be a novel therapeutic target for restoring aging-associated impairments in stem cell function.