Adipose-derived stem/stromal cells in kidney transplantation: Status quo and future perspectives

Kidney transplantation (KT) is the gold standard treatment of end-stage renal disease. Despite progressive advances in organ preservation, surgical technique, intensive care, and immunosuppression, long-term allograft survival has not significantly improved. Among the many peri-operative complications that can jeopardize transplant outcomes, ischemia-reperfusion injury (IRI) deserves special consideration as it is associated with delayed graft function, acute rejection, and premature transplant loss. Over the years, several strategies have been proposed to mitigate the impact of IRI and favor tolerance, with rather disappointing results. There is mounting evidence that adipose stem/stromal cells (ASCs) possess specific characteristics that could help prevent, reduce, or reverse IRI. Immunomodulating and tolerogenic properties have also been suggested, thus leading to the development of ASC-based prophylactic and therapeutic strategies in pre-clinical and clinical models of renal IRI and allograft rejection. ASCs are copious, easy to harvest, and readily expandable in culture. Furthermore, ASCs can secrete extracellular vesicles (EV) which may act as powerful mediators of tissue repair and tolerance. In the present review, we discuss the current knowledge on the mechanisms of action and therapeutic opportunities offered by ASCs and ASC-derived EVs in the KT setting. Most relevant pre-clinical and clinical studies as well as actual limitations and future perspective are highlighted.