원문정보
초록
영어
Stem cells offer therapeutic promise for the treatment of ischemic disease. However, stem cell treatment exhibit limited therapeutic efficacy due to poor engraftment in vivo. Here, we demonstrate that human adipose-derived stem cells (hADSCs) cultured and grafted as spheroids exhibit improved therapeutic efficacy for ischemia disease. Spheroid cultures were more effective in preconditioning hADSCs to a hypoxic environment, upregulating hypoxia-adaptive signals and enhancing secretion of both angiogenic and anti-apoptotic factors compared to monolayer cultures. Moreover, spheroids cell harvesting procedure enabled us to avoid damage caused by harsh proteolytic enzyme treatments. Transplantation of hADSC into ischemica region, hADSC spheroids showed improved cell survival, neovascularization, and limb survival as compared to grafted as dissociated cells. Spheroid cultures prime hADSCs to a hypoxic environment and grafting hADSCs as spheroids to ischemic limbs improve therapeutic efficacy for ischemia treatment due to enhanced cell survival and paracrine effects. Spheroid cell delivery could be a simple and effective strategy for improving stem cell therapy for ischemic diseases.