MSC-based therapies in solid organ transplantation

Immunomodulatory cell therapy as a complement to standard pharmacotherapy represents a novel approach to solid organ allograft acceptance. This methodology may allow for a reduced dose of immunosuppressive drug to be administered and thus attenuate the severe side effects associated with long-term immunosuppression such as drug-related impairment of renal function, increased risk from opportunistic infections and malignancies. Mesenchymal stem cells (MSCs) have been shown to possess both immune modulatory and regenerative properties in vitro and in preclinical models. Encouraging results have been reported from studies examining the safety and efficacy of MSCs as a treatment for acute graft-versus-host disease. MSCs represent a promising candidate cell therapy to supplement immunosuppression in recipients of solid organs, and initial reports on the clinical use of MSCs in kidney transplantation have been recently published (Tan et al. in J Am Med Assoc 307:1169-1177, 2012; Reinders et al. in Stem Cells Transl Med 2:107-111, 2013; Perico et al. in Transpl Int 26:867-878, 2013; Perico et al. in Clin J Am Soc Nephrol 6:412-422, 2011). An area of even greater interest might be the application of MSCs in clinical liver transplantation as graft survival is closely associated with overall patient survival. Here, we present preclinical findings and discuss their possible impact on clinical liver transplantation. Then we discuss clinical studies designed to investigate how MSCs may be distributed and act in solid organ transplantation.