The Unique Immunomodulatory Properties of MSC-Derived Exosomes in Organ Transplantation

Abstract

Methods for suppressing the host immune system over the long term and improving transplantation tolerance remain a primary issue in organ transplantation. Cell therapy is an emerging therapeutic strategy for immunomodulation after transplantation. Mesenchymal stem cells (MSCs) are adult multipotent stem cells with wide differentiation potential and immunosuppressive properties, which are mostly used in regenerative medicine and immunomodulation. In addition, emerging research suggests that MSC-derived exosomes have the same therapeutic effects as MSCs in many diseases, while avoiding many of the risks associated with cell transplantation. Their unique immunomodulatory properties are particularly important in the immune system-overactive graft environment. In this paper, we review the effects of MSC-derived exosomes in the immune regulation mechanism after organ transplantation and graft-versus-host disease (GvHD) from various perspectives, including immunosuppression, influencing factors, anti-inflammatory properties, mediation of tissue repair and regeneration, and the induction of immune tolerance. At present, the great potential of MSC-derived exosomes in immunotherapy has attracted a great deal of attention. Furthermore, we discuss the latest insights on MSC-derived exosomes in organ transplantation and GvHD, especially its commercial production concepts, which aim to provide new strategies for improving the prognosis of organ transplantation patients.

Mesenchymal Stem Cell-Derived Exosomes and Their Potential Agents in Hematological Diseases

“…Once this critical function was reported, the interest to unearth the interactions between MSC-exosomes with microenvironmental niche underwent a new upsurge [ 60 , 67 , 77 ]. Among these intricate and complex relationships in which MSC-exosomes participate, the key pathological processes such as inflammation, oxidative stress, antitumor effect, and regenerative nature have drawn wide attention ( Figure 2 ) [ 2 , 12 , 28 , 35 , 46 ].…”

“…Currently, MSC therapies are underway, and their properties of multipotentiality and low immunogenicity have made them promising cell-based strategies for various types of clinical applications [ 27 , 28 , 42 ]. However, their beneficial effects have been hampered due to the capacity that unexpectedly differentiate or uncontrollably grow in the hosts [ 92 ].…”

Bone marrow mesenchymal stem cell-derived exosomes attenuate the maturation of dendritic cells and reduce the rejection of allogeneic skin transplantation in mice model

“…Due to their potential applications in enabling alloantigen tolerance, MSCs have been investigated thoroughly and found to exert an immunomodulatory effect that in uences all cells involved in the immune response 23 . Moreover, the paracrine effect is one of the critical mechanisms of MSCs underlying immune tolerance 24 .…”

“…Bruno et al 25 demonstrated that exosomes play a signi cant role in the paracrine effect of MSCs. As a tool of cell-to-cell communication, exosomes transfer biological material between the cells in the form of paracrine and remote secretion and regulate the physiological and pathological conditions 23 . Several studies have shown that MSC-derived exosomes are enabled to affect the activity of immune cells, including T cells, B cells, NK cells, and macrophages.…”

“…However, our cell injection strategy could not achieve long-term transplant survival. Notably, it is di cult to achieve tolerance or long-term survival without the use of immunosuppressants 23 . However, tolDCs combined with suboptimal doses of immunosuppressants may achieve speci c allograft tolerance and long-term transplant survival 37 .…”