Possible Protective Effect of Bone Marrow-Mesenchymal Stem Cells (BM-MSCs) Against the Remote Liver Injury Induced by Renal Ischemia Reperfusion in Male Albino Rats
Received Date: Oct 01, 2017 / Accepted Date: Nov 05, 2017 / Published Date: Nov 13, 2017
Background: Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal injury and leads to multiorgan dysfunction especially liver injury. Stem cell therapy has been used effectively in treatment of renal IRI.
Aim of the work: To investigate the possible therapeutic effect of BM-MSC therapy on the remotely affected liver in a rat model of renal IRI and the mechanisms involved in this effect.
Methods: Rats were divided into 3 groups; the sham-operated control group, the renal IRI group: bilateral renal IRI for 45 minutes followed by reperfusion, and BM-MSCs-injected group: rats were subjected to renal IRI and then received a single intravenous (iv) injection of BM-MSCs immediately after reperfusion. At the different time-points (days 1, 3, and 5) of the study, serum urea, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were estimated. Livers were removed and were divided: some specimens were homogenized for assessment of oxidant and antioxidant parameters, and other specimens were used for paraffin embedding for histological and immunohistochemical study.
Results: Renal IRI resulted in a significant increase in serum levels of urea, creatinine, AST, ALT, and hepatic tissue levels of malondialdehyde (MDA) which attenuated on days 3 and 5 after BM-MSCs injection. MDA showed an early significant decrease in the BM-MSCs-injected group at day 1. Reduced glutathione (GSH) showed a significant decrease in the IRI sub-groups while BM-MSCs-injected sub-groups showed significantly higher levels of GSH on days 1, 3 and 5. Tissue sections showed that labeled BM-MSCs were engrafted into liver tissue. The IRI subgroups showed marked destruction of liver tissue e.g. disrupted lobular architecture, marked hepatocellular ballooning and cytoplasmic vaculations, and marked recruitment of the inflammatory cells with vascular congestion. While in the BM-MSCs-injected subgroups, there were gradual regeneration and restoration of lobular architecture, reduced degenerated cells, decreased congestion, and minimal inflammatory cell infiltration. By day 5, most hepatocytes had more or less normal appearance, arranged in cords with preserved general architecture and lacking evidence of major morphological injury. In addition, BM-MSCs significantly attenuated the liver immunohistochemical expression of tumor necrosis factor-alpha (TNF-α).
Conclusion: BM-MSCs protects against the remote liver injury induced by renal IRI through early inhibition of inflammatory cell recruitment, inflammatory reactions, suppressing oxidative stress and lipid peroxidation, and rapid restoration of cellular and architectural integrity of the liver. This provides another important basis for the therapeutic concept of BM-MSCs in treatment of renal IRI by adding a beneficial effect on decreasing the remote liver injury besides considering it as a promising treatment in renal IRI.
Keywords: Remote liver injury; Renal ischemia reperfusion; Mesenchymal stem cells; immunohistochemistry; TNF-α
Citation: El-Tahawy NFG, Ali AHSA (2017) Possible Protective Effect of Bone Marrow-Mesenchymal Stem Cells (BM-MSCs) Against the Remote Liver Injury Induced by Renal Ischemia Reperfusion in Male Albino Rats. J Cytol Histol 8: 484. Doi: 10.4172/2157-7099.1000484
Copyright: © 2017 El-Tahawy NFG, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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