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. STATEMENT OF SIGNIFICANCE: It remains a challenge to efficiently deliver stem cells to target tissues, which may limit the clinical application of stem cell-based therapy. In this study, we developed a modified strategy of decellularization and gelation to prepare the kidney extracellular matrix hydrogel (ECMH). In vivo and in vitro evidence indicated that the kidney ECMH could improve the retention and survival rate, as well as multiple biological functions of adipose-derived mesenchymal stem cells, thereby contributing to the histological and functional recovery of injured kidneys induced by ischemia-reperfusion. Our findings highlight the use of organs or tissues derived ECMH as a promising stem cell delivery scaffold for tissue repair.

Keywords: Adipose-derived mesenchymal stem cells; Extracellular matrix; Hydrogel; Renal ischemia reperfusion injury; Stem cell-based therapy.