Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis

Abstract

Background and AimsTo evaluate the effect of intraparenchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC).MethodsMononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation.ResultsOn clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and α-SMA in liver biopsy samples were decreased at 6 months after transplantation, consistent with structural improvements in mitochondria and nuclear compartments.ConclusionsIntraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation.

Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

“…The infection of hepatitis C virus (HCV) can cause liver cirrhosis and degeneration of hepatic tissue. The intraparenchymal transplantation of bone marrow mononuclear cells (BMMNCs) into liver tissue decreases aspartate aminotransferase (AST), alanine transaminase (ALT), bilirubin, CD34, and α -SMA, suggesting that transplanted BMSCs restore hepatic functions through regeneration of hepatic tissues [ 113 ]. In order to meet the growing demand for stem cells transplantation therapy, donor encouragement is always required [ 8 ].…”

Mesenchymal Stromal Cells: an Antimicrobial and Host-Directed Therapy for Complex Infectious Diseases

“…In HCV-related liver cirrhosis, autologous BM-MSCs were administered to the liver parenchyma of six patients in a nonrandomized, noncontrolled phase 1 trial (264). MSCs were well tolerated, with jaundice resolving in four of six patients after 6 months and a reduction of transaminitis, although this reduction did not reach statistical significance.…”

Stem Cell Therapies for Treatment of Liver Disease

“…When compared to granulocyte-colony-stimulating factor mobilization therapy alone, peripheral blood monocyte transplant therapy offered a significant improvement in liver function as measured by albumin levels and Child-Pugh scores [ 113 ]. Another study found that after intraparenchymal autologous mesenchymal bone marrow-derived stem cell transplantation in hepatitis C patients, the liver showed structural improvement as evidenced by its decreased extracellular matrix protein count on biopsy [ 114 ]. Hepatitis C patients have also been treated with peripheral injection of autologous MSCs, with MELD score improvement but no change in liver fibrosis or regeneration on histopathological examination at six months post-treatment.…”