Regenerative Capacity of Transplanted Mesenchymal Versus Mononuclear Stem Cells in Carbon Tetrachloride Induced Liver Injury in Rats
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- Category: Vol. 84, June 2016
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Regenerative Capacity of Transplanted Mesenchymal Versus Mononuclear Stem Cells in Carbon Tetrachloride Induced Liver Injury in Rats, NOHA R. NOUFAL, MOHAMED O. EL-OKDA, HOWAYDA S. ABD EL-ALL, YASSER EL-WAZIR and FADIA M. ATTIA
Abstract
Aim of the Work: Our study aimed at investigation of the capacity of allogenic bone marrow derived Mesenchymal Stem Cells (MSCs) versus Mononuclear Stem Cells (MNSCs) to regenerate liver in carbon tetrachloride (CCl4) animal model of liver fibrosis. The role of regulatory T cells (CD4+ & IL2a/CD25+) in controlling homing of the transplanted stem cells was also evaluated.
Animal: After induction of liver fibrosis for 8 weeks, the survived female rats were divided into positive control group (CO+) and two groups treated with MSCs and MNSCs isolated from Sprague Dawley male rats. To provide independent evidence of homing of transplanted male donor cells, real time PCR was done to detect sex determining region on the Y chromosome (Sry) gene. N-terminal Procollagen III (PII-INP), liver function test (alanine aminotransferase ALT, aspartate aminotransferase AST, Gamma Glutamyl Transferase GGT and Albumin Alb) were assessed. Histopatological examination of livers was done to evaluate the regeneration of hepatocytes and improvement of fibrosis. Expression of CD4 and IL2a/CD25 was also evaluated.
Results: In group received MSCs, Sry gene was detected in 100% of rats and in 84.6% of MNSCs treated group. Serum concentration of PIIINP showed good improvement in group treated with MSCs (160.938±33.741), compared to MNSCs (190.582±27.842) after 8 weeks of transplantation. Compared to CO+, liver functions (ALT, AST and GGT) were improved in treated groups in time dependent fashion. The group received MSCs showed good improvement compared to MNSCs treated group. After 8 weeks of MSCs transplantation 42.7% of rats showed resolution of fibrosis with variable improvement of hepatitis activity. 57.1% of rats treated with MNSC for 8 weeks showed improvement of the hepatitis to milder degrees of activity and resolutions of fibrosis. Cytoplasmic expression of CD4 and IL2a/CD25 was positive in most of animals which received MSCs and MNCSs. There was significant correlation between CD4 and IL2a/CD25 in both groups.
Conclusion: MSCs are capable of regeneration of hepa-tocytes and restoration of hepatic architecture compared to MNSCs. Expansion of regulatory T cells played an important role in homing of MSCs and improving the immunomodulatory properties of MSCs.