Molecular mechanisms responsible for mesenchymal stem cell–dependent improvement of islet cell transplantation

Islet cell transplantation holds great promise for restoring glycemic control in patients with type 1 diabetes. However, its long-term efficacy remains limited due to poor islet survival, immune rejection, and insufficient vascularization. Mesenchymal stem cells (MSCs) have emerged as potent biological adjuvants capable of addressing these challenges through a range of molecular mechanisms. MSCs secrete a variety of growth factors, immunoregulatory and pro-angiogenic molecules that enhance viability of islet cells, modulate the immune response, promote neo-angiogenesis and enhance islet engraftment. In addition, MSC-derived exosomes (MSC-Exos) have been identified as key mediators, delivering regulatory microRNAs and proteins that replicate many of the beneficial effects of MSCs in a cell-free format. MSC-Exos act as small RNA carriers and immunomodulators, promoting islet survival and functional integration. Understanding the molecular interplay between MSCs, their exosomes, and the islet microenvironment provides crucial insights for the development of advanced co-transplantation strategies. Accordingly, in this review article, we summarized current knowledge about molecular mechanisms that are responsible for MSC-dependent improvement of islet cell transplantation and we highlighted the translational potential of MSC and MSC-Exos-based approaches in improving islet graft outcomes for type 1 diabetes.