Kidney extracellular matrix hydrogel enhances therapeutic potential of adipose-derived mesenchymal stem cells for renal ischemia reperfusion injury.

Abstract Stem cell-based therapy has been suggested as a promising option for the treatment of renal ischemia-reperfusion injury (IRI). However, how to efficiently deliver stem cells remains a challenge. In the present study, we firstly proposed the utilization of kidney extracellular matrix hydrogel (ECMH) as an injectable scaffold for delivering adipose-derived mesenchymal stem cells (ad-MSCs) into ischemic kidneys. A modified strategy of decellularization and gelation was introduced to prepare the ECMH, by which the bioactive ingredients were retained as much as possible. Bioluminescence living imaging and immunofluorescence revealed that ECMH could significantly elevate the retention and survival rate of transplanted ad-MSCs in damaged kidneys and reduce their escape rate to other organs, which consequently resulted to the enhanced therapeutic effect of ad-MSCs on renal IRI. Further, in vitro evidence demonstrated that ECMH could remarkably reduce the oxidative stress and apoptosis, promote the proliferation, secretion, and epithelial differentiation of ad-MSCs, as well as facilitate cell migration while acting as a sustained-release scaffold. This study establishes an effective approach to enhance the therapeutic potential of ad-MSCs for renal IRI. Our findings suggest that ECMH derived from organs or tissues would be a promising injectable scaffold for stem cell-based therapy.