A hydrogel platform delivering mesenchymal stem cell lysate for potential myocardial tissue repair.

INTRODUCTION: Myocardial infarction is one of the most significant causes of death worldwide and the limited regenerative capacity of the myocardium often results in poor recovery after injury. Stem cell therapy has some promise for myocardial tissue repair, but clinical translation is hindered by poor cell survival and safety concerns, prompting the investigations of cell-free strategies such as stem cell-derived secretome or lysate. METHODS: In this study, a quaternized chitosan/tannic acid hydrogel was fabricated and characterized for its crosslinking stability, injectability and degradation kinetics. In addition, mouse adipose-derived mesenchymal stem cells (mADSCs) were isolated, characterized, and processed into cell-free lysate. The mADSCs lysate was then analyzed by TEM, NTA, Western blot and enzyme-linked immunosorbent assay. RESULTS: It was found that the mADSCs lysate contained abundant vesicles and a broad panel of cytokines/growth factors with anti-inflammatory, pro-angiogenic and antioxidant properties. Encapsulating the lysate within the hydrogel showed sustained release. The hydrogel-based delivery of mADSCs lysate could promote high metabolic activity and good cell number increases of H9c2-cardiomyocytes, L929-fibroblasts and human umbilical vein endothelial cells, demonstrating great potential for myocardial tissue repair applications. DISCUSSION: By integrating the regenerative potential of ADSCs lysate with this biocompatible, injectable hydrogel platform, this combined strategy circumvents the potential safety issues associated with live cell transplantation and offers a scalable, potential cell-free delivery strategy for myocardial repair-related applications, laying a foundation for future in vivo studies and further translational evaluation.