An injectable decellularized matrix that improves mesenchymal stem cell engraftment for therapeutic angiogenesis

Abstract

Stem cell therapy has great potential for the treatment of ischemic diseases, but poor engraftment of implanted stem cells limits the therapeutic efficacy. Here, we developed an approximately 80 mu m injectable decellularized matrix (IDM) to increase the angiogenic efficacy of mesenchymal stem cells by improving the engraftment of the stem cells implanted in to an ischemic tissue. Adhesion of human adipose tissue-derived stem cells (hADSCs) to the IDM enhanced the cell viability and upregulated angiogenic factors in vitro under either cell adhesion-suppressive conditions or hypoxic conditions, which simulated the microenvironment of ischemic tissues. In a murine ischemic-hindlimb model, hADSCs that were attached to the IDM and subsequently injected into an ischemic region showed better grafting and angiogenic factor expression. The hADSC-IDM implantation subsequently promoted the formation of microvessels, attenuated fibrosis, and increased blood perfusion in the ischemic region, as compared to implantation of hADSCs only. The IDM may be an effective off-the-shelf material that can enhance therapeutic efficacy of stem cell therapy for ischemic diseases.