MSC-based therapies in solid organ transplantation

Abstract

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.

Identification of Pathways in Liver Repair Potentially Targeted by Secretory Proteins from Human Mesenchymal Stem Cells

“…The biological features of mesenchymal stem cells (MSC) make them feasible candidates for cellular therapy for a variety of diseases, e.g., acute kidney injury, brain repair after stroke, colitis [ 1 , 2 , 3 , 4 , 5 , 6 ], and acute and chronic liver diseases [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Depending on the therapeutic goal, MSC might be used as undifferentiated cells to provide regenerative support by paracrine actions or after hepatocytic differentiation to provide metabolic capacity, or to bridge the patient to liver transplantation [ 15 ].…”

Exosomes: Potential executors of IL‐35 gene‐modified adipose‐derived mesenchymal stem cells in inhibiting acute rejection after heart transplantation

“…How to establish immune tolerance to avoid the complications caused by long-term use of immunosuppressants has become the ultimate goal in the field of transplantation. In many explorations, MSC-based therapy has attracted increasing attention in solid organ transplantation, [21][22][23][24] especially genetic modification, which has enhanced the therapeutic effects of MSCs and greatly expanded their therapeutic prospects. [25][26][27] However, accumulating evidence suggests that MSCs exert their therapeutic effects, which is mainly attributed to their ability to interact with injured tissues by releasing soluble bioactive factors (ie paracrine function), rather than long-term integration into host tissues.…”

Pediatric Mesenchymal Stem Cells Exhibit Immunomodulatory Properties Toward Allogeneic T and B Cells Under Inflammatory Conditions

“…Due to their multipotent differentiation and immune modulation properties, MSCs have been successfully investigated for their use in several diseases such as ischemia (Cortez-Toledo et al, 2018), autoimmune diseases (Gerdoni et al, 2007; González et al, 2009), as well as in solid organ transplantation (Benseler et al, 2014). Other applications of MSCs include their potential use in tissue engineering and regenerative medicine (Barry and Murphy, 2013; Shao et al, 2015).…”