Role of Regulatory T-Cells in Stem Cell Homing in A Rat Model of Liver Fibrosis: A Comparative Study between Rat Bone Marrow Derived Mesenchymal and Hematopoietic Stem Cells
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- Category: Vol. 84, June 2016
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Role of Regulatory T-Cells in Stem Cell Homing in A Rat Model of Liver Fibrosis: A Comparative Study between Rat Bone Marrow Derived Mesenchymal and Hematopoietic Stem Cells, NOHA R. NOUFAL, MOHAMED O. EL-OKDA, HOWAYDA S. ABD EL-ALL, YASSER EL-WAZIR and FADIA M. ATTIA
Abstract
Aim of the Work: Investigation of the effectiveness of allogeneic bone marrow derived mesenchymal (MSCs) and Hematopoietic (HSCs) stem cells transplantation in regener-ation of hepatocytes and to evaluation the role of regulatory T cells (CD4+ & IL2a/CD25+) in controlling their homing in rat model of liver fibrosis.
Material: After 8 weeks of Carbon Tetrachloride (CCl4) induction of liver fibrosis, the survived Sprague Dawley female rats were divided into positive control group (CO+) and two groups treated with MSCs and HSCs (Thy1.1+/ CD90.1) isolated from male rats. Real time PCR was done to detect sex determining region on the Y chromosome (Sry) gene on sacrificed rats liver after 8 weeks of transplantation. N-terminal procollagen III (PIIINP), liver function test (Alanine aminotransferase ALT, Aspartate aminotransferase AST, Gam-ma glutamyl transferase GGT and Albumin Alb were assessed. Histopatological examination of livers was done. Expression of CD4 and IL2a/CD25 was also evaluated.
Results: Sry gene was detected in 100% of rats received MSCs and in 84.6% of HSCs treated group. Serum concen-tration of PIIINP showed good improvement in group treated with MSCs (160.938±33.741) compared to HSCs (185.472± 35.762) after 8 weeks of transplantation. Liver functions (ALT, AST and GGT) were improved in the treated groups compared to CO+ in time dependent fashion. The mean levels of liver enzymes showed good improvement of group received MSCs compared to HSCs treated group. There was significant difference between the mean levels of ALT and AST of group treated with MSCs for 6 and 8 week. Albumin level remained within the normal ranges. Improvement of necroinflammatory changes with restoring hepatic architecture was noted in 51.7% of group received HSCs. After 8 weeks of MSCs transplantation 42.7% of rats showed resolution of fibrosis with variable improvement of hepatitis activity. Cytoplasmic expression of CD4 and IL2a/CD25 was positive in 42.8% of animals which received MSCs while more than half of animals received HCSs showed no expression.
Conclusion: MSCs are capable of regeneration of hepa-tocytes and restoration of hepatic architecture compared to HSCs. Expansion of regulatory T cells played an important role in homing of MSCs and improving the immunomodulatory properties of MSCs.