Role of Stem Cell Therapy in Management of Hepatic Pathology

Abstract

Although SCs are a promising means for treatment of liver diseases, studies are still at the beginning of this era. Results of experimental animals and clinical trials are still preliminary. While all clinical trials to date have shown some improvement in liver function, it ought to be remembered that the natural history of cirrhosis tends to be variable.The major role for SCs therapy is as a bridge to transplantation or as a way of maintaining those patients who are not eligible for liver transplant. The long-term safety, tolerability, and efficacy of these SCs-based treatments, as well as their carcinogenic potential must be considered. New clinical trials are needed. Various clinical studies for liver disease have been reported, including hepatic administration of autologous CD34-positive cells induced by G-CSF, portal vein administration of CD133-positive mononuclear cells, and administration of autologous bone marrow derived mesenchymal SCs. Effectiveness of these approaches has been shown in some patients. Also, experimental studies have reported improved liver fibrosis and function with infusion of autologous bone marrow cells in a basic study with mice. The efficacy and safety of autologous bone marrow cell infusion (ABMI) therapy has also been reported by other Institutions. Isolation of hepatic progenitors from a human source is a major challenge for the clinical application of this therapy. Intrahepatic sources include cadaver livers that are considered of insufficient quality for organ transplantation. Hepatocytes isolated from aborted human fetuses are another potential source. Extra-hepatic sources include autologous bone marrow, umbilical cord blood, Wharton’s jelly, and peripheral blood monocytes. Results of recent clinical studies strongly suggest that liver function-improving effects can be achieved using infusion of bone marrow SCs for cirrhosis. New treatment methods using less-invasive bone marrow-derived cultured cells need to be developed. New findings in adult stem cell biology are transforming our understanding of tissue repair raising hopes of successful regenerative hepatology. Although all clinical trials to date have shown some improvement in liver function and CD34+ cells have been used safely for BM transplantation for over 20 years, only randomized controlled clinical trials will be able to fully assess the potential clinical benefit of adult stem cell therapy for patients with liver insufficiency. Conversely, concerns have been raised about the adverse long-term effects of stem cell therapy. There is evidence to suggest that treatment with BMSCs may provide liver fibrogenic cells (hepatic stellate cells and myo-fibroblasts) which contribute to fibrosis and could have a deleterious effect on already decompensated cirrhotic livers. The optimal SCs delivery route should be easy to perform, less invasive and traumatic minimum side effects, and with high cells survival rate. Liver SCs can be transplanted through several routes: Intraperitoneal and percutaneous intrahepatic artery catheterization in acute liver failure, and umbilical vein catheterization, percutaneous intrahepatic route, and portal vein or intrahepatic artery catheterization in metabolic liver diseases. Intrasplenic artery, hepatic artery and portal vein catheterization in chronic liver diseases. Whatever the source or delivery route of SCs, how they can be manipulated for therapeutic interventions in a variety of hepatic diseases is of course of great interest in future studies. The selected methodology to purify stem cells is an importantconsideration in order to guarantee success regarding purity andviability that determines the positive outcome of the therapies. Currently, there is neither satisfactory technique nor strategy that allows the full practical separation of stem cells at large scale. Therefore, there is a great need to focus research in the field on the development of a suitable separation and purification technology for stem cells to establish a manufacturing process, which is fundamental to avoid a delay in the widespread application of stem cells therapy. This therapy has been proposed as a promising treatment for diseases for which no cure is available.