Abstract
Although liver transplantation is considered to be the best choice for patients with end-stage liver diseases, postoperative immune rejection still cannot be overlooked. Patients with liver transplantation have to take immunosuppressive drugs for a long time or even their entire lives, in which heavy economic burden and side effects caused by the drugs have become the major impediment for liver transplantation. There is a growing body of evidences indicating that mesenchymal stem cell (MSC) transplantation, a promising tool in regenerative medicine, can be used as an effective way to induce immune tolerance after liver transplantation based on their huge expansion potential and unique immunomodulatory properties. MSCs have been reported to inhibit innate immunity and adaptive immunity to induce a tolerogenic microenvironment. In in vitro studies, transplanted MSCs show plasticity in immune regulation by altering their viability, migration, differentiation, and secretion in the interactions with the surrounding host microenvironment. In this review, we aim to provide an overview of the current understanding of immunomodulatory properties of MSCs in liver transplantation, to elucidate the potential mechanisms behind MSCs regulating immune response, especially in vivo and the influence of the microenvironment, and ultimately to discuss the feasible strategies to improve the clinical prognosis of liver transplantation. Only after exhaustive understanding of potential mechanisms of the MSC immunomodulation can we improve the safety and effectiveness of MSC treatment and achieve better therapeutic effects.
Highlights
As the most important detoxification organ, the liver is supplied by dual blood supply and may eventually develop into end-stage disease, such as decompensated liver cirrhosis, liver failure, or hepatocellular carcinoma after long-term exposure to a variety of intestinal toxins, metabolic products, or exogenous pathogens [1]
We aim to provide an overview of the current understanding of immunomodulatory properties of mesenchymal stem cell (MSC) in liver transplantation, to elucidate the potential mechanisms behind MSCs regulating immune response, especially in vivo and the influence of the microenvironment, and to discuss the feasible strategies to improve the clinical prognosis of liver transplantation
A phase I-II, open-label, clinical study published in J Hepatol in 2017 [40] indicated different findings that MSC infusion was unable to induce immune tolerance after liver transplantation and it was not successful to achieve immunosuppression weaning in MSC recipients; there was no significant difference in overall rates of rejection and graft survival, peripheral blood lymphocyte typing, and 6-onth graft biopsies between two groups, and this result might be owning to small sample size (n = 10), the tacrolimus-based immunosuppressive regimen, or insufficient dosage of MSCs
Summary
As the most important detoxification organ, the liver is supplied by dual blood supply and may eventually develop into end-stage disease, such as decompensated liver cirrhosis, liver failure, or hepatocellular carcinoma after long-term exposure to a variety of intestinal toxins, metabolic products, or exogenous pathogens [1]. Liver transplantation has been considered to be the only effective treatment for patients with end-stage liver diseases. There are no large-scale clinical practices involving MSCs for liver transplantation and most investigations on MSCs remain in the preclinical stage, the unique immunomodulatory properties of MSCs shown in recent studies make MSC transplantation a promising tool in regenerative medicine to induce immune tolerance to various immunerelated diseases [8,9,10,11]. We aim to provide an overview of the current understanding of immunomodulatory properties of MSCs in liver transplantation, to elucidate the potential mechanisms behind MSCs regulating immune response, especially in vivo and the influence of the microenvironment, and to discuss the feasible strategies to improve the clinical prognosis of liver transplantation. After exhaustive understanding of potential mechanisms of the MSC immunomodulation can we improve the safety and effectiveness of MSC treatment and achieve better therapeutic effects
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