Effect of Bone Marrow-derived Mesenchymal Stem Cells and Umbilical Cord Blood-CD34+ cells on Experimental Rat liver Fibrosis

Abstract

Background and Objective: Liver disease is one of the major causes of death in many countries. Hence, the development of effec- tive therapies for liver fibrosis is a major aim of medical research. So this study was designed to investigate the therapeutical role of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) transplantation in the experimental rat liver fibrosis. Design and Method: Bone marrow-derived MSCs were isolated from femoral and tibial bones of male albino rats, then were grown and propagated in culture for 2 weeks and were characterized morphologically and by detection of CD29 by real time-PCR. Hu- man umbilical cord blood cells were obtained after full-term caesarean delivery from healthy donors after written informed consent. Low-density mononuclear cells were separated over Ficoll- Paque (Gibco-Invitrogen, Grand Island, NY), and then CD34+ HSC was isolated using a magnetic cell sorter (MiniMACS; Miltenyi Biotec, Bergisch Gladbach, Germany). The cells were then infused intraperi- toneally in rats that received CCl4 injection to induce liver fibrosis. Rats were divided into 4 groups: control, CCl4, CCl4 plus MSC, and CCl4 plus CD34+. Liver tissue was examined histopathologically for all groups. The expression of collagen I and metalloproteinase-2 genes as a marker of liver fibrosis was measured by real time RT- PCR. Results: The results of the present study showed that both MSCs and CD34+ have a significant antifibrotic effect as evidenced by the significant decrease in liver collagen gene expression as well as the decrease in MMP-2 (p < 0.05) compared to the CCl4 group.