Injectable Glucose-Releasing Microgels Enhance the Survival and Therapeutic Potential of Transplanted MSCs Under Ischemic Conditions

Mesenchymal stem cell (MSC)-based therapies show potential to treat ischemic diseases owing to their versatile functions. However, sustaining MSC viability and therapeutic efficacy in ischemic tissues postengraftment remains a significant challenge. This is because, although MSCs are metabolically flexible, they fail to adapt to hypoxic conditions in the absence of glucose, leading to cell death. To overcome these issues, it is aimed to establish an injectable glucose delivery system using starch and amyloglucosidase embedded in alginate microgels. Here, starch/amyloglucosidase (S/A) microgels are engineered to continuously release glucose for seven days via enzymatic hydrolysis, thereby supporting MSC functions under ischemic conditions. In vitro tests under oxygen/glucose-deprived conditions revealed that the S/A microgels not only maintained the viability and intracellular energy but also enhanced the pro-angiogenic and immunomodulatory functions of MSCs. In vivo data further confirmed the pro-survival and pro-angiogenic effects of S/A microgels on MSCs following subcutaneous engraftment in mice. Overall, the developed S/A microgel significantly enhanced the survival and therapeutic potential of MSCs via sustained glucose delivery, highlighting its potential use in advancing MSC-based therapies for ischemic conditions.