Exogenous MSC based tissue regeneration: a review of immuno-protection strategies from biomaterial scaffolds.

Mesenchymal stem cell (MSC)-based tissue engineering holds great potential for regenerative medicine as a means of replacing damaged or lost tissues to restore their structure and function. However, the efficacy of MSC-based regeneration is frequently limited by the low survival rate and limited survival time of transplanted MSCs. Despite the inherent immune privileges of MSCs, such as low expression of major histocompatibility complex antigens, tolerogenic properties, local immunosuppressive microenvironment creation, and induction of immune tolerance, immune rejection remains a major obstacle to their survival and regenerative potential. Evidence suggests that immune protection strategies can enhance MSC therapeutic efficacy by prolonging their survival and maintaining their biological functions. Among various immune protection strategies, biomaterial-based scaffolds or cell encapsulation systems that mediate the interaction between transplanted MSCs and the host immune system or spatially isolate MSCs from the immune system for a specific time period have shown great promise. In this review, we provide a comprehensive overview of these biomaterial-based immune protection strategies employed for exogenous MSCs, highlighting the crucial role of modulating the immune microenvironment. Each strategy is critically examined, discussing its strengths, limitations, and potential applications in MSC-based tissue engineering. By elucidating the mechanisms behind immune rejection and exploring immune protection strategies, we aim to address the challenges faced by MSC-based tissue engineering and pave the way for enhancing the therapeutic outcomes of MSC therapies. The insights gained from this review will contribute to the development of more effective strategies to protect transplanted MSCs from immune rejection and enable their successful application in regenerative medicine.