Bone marrow mononuclear cell therapy for patients with cirrhosis: a Phase 1 study

Abstract

BMMCs infusion is feasible and practical in a clinical setting. In vivo tracking of labelled cells demonstrated that the hepatic artery route successfully delivered BMMCs to the liver. The early improvement of laboratory indices of liver function should be interpreted with caution, because this study was not designed to evaluate efficacy. The median Model for End-Stage Liver Disease score had not deteriorated 1 year later. The occurrence of a graft-versus-host disease-like phenomenon highlights the importance of sustained vigilance even when giving autologous cells. Controlled studies are needed to determine whether BMMCs infusion affects HCC development in cirrhosis.

Therapeutic Strategies of Stem Cell Transplantation for Liver Cirrhosis

“…However, the reduced cellular immune response was usually found in the patients of alcoholic liver cirrhosis complicated with HCV [6], hence the HSCs transplantation did not result in any adverse effect related to the immune response, which has been confirmed by Couto BG [9]. Depressed cellular immune function is often shown in patients with HBV-or HCV-induced cirrhosis [11].…”

“…The type of stem cells should be selected cautiously and carefully to avoid enhancing the immune response and triggering an immune system disorder [3] [4] [8] [9]. MSCs is preferred over HSCs for the cirrhosis with the severe inflammation.…”

“…As a result of this disease profile, HSCs are eliminated by the active immune cells during the treatment of early-stage alcoholic liver cirrhosis, and accompanied by exacerbating the progression of hepatic fibrosis [8]. A previous study shows that two among eight patients receiving HSCs for the treatment of alcoholic liver cirrhosis, there was one case of diabetes (an autoimmune disease) with graft-versus-host disease, and another patient developed deterioration of liver function with the hemorrhage of the upper digestive tract [9]. Jang et al [10] treated alcoholic cirrhosis with MSCs and found no adverse events.…”

New horizons for stem cell therapy in liver disease

“…Whilst no studies report superior outcomes when cells are directly injected into the liver (portal vein or hepatic artery), there have been complications such as hepatic artery dissection [19] and increased portal hypertensive bleeding [20] following this approach. Furthermore, the intravenous administration of autologous BM mononuclear cells resulted in hepatic homing of the injected cells suggesting this easier, safer route may be an adequate option for cell delivery [9,21].…”

Bone Marrow-Derived Mononuclear Cells Differentiate into Hepatocyte-Like Cells within Few Hrs without Fusion

“…In models of acute liver failure, transplantation of these cells increase the survival rate [1,2]. Furthermore, recent clinical trials have demonstrated that transplantation of these cells or their fractions improves the condition of patients with cirrhosis [3][4][5], as well as improve liver function in animal models of cirrhosis [6]. Moreover, BMMC are characterized by their ability to differentiate into several functional mature cell types both in vivo and in vitro, including cardiomyocytes [7,8], endothelial cells [9], neurons [10,11] and hepatocytes [12][13][14][15][16][17][18].…”