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Melatonin Pretreatment Enhances the Homing of Bone Marrow-Derived Mesenchymal Stem Cells Following Transplantation in a Rat Model of Liver Fibrosis Publisher Pubmed



Mortezaee K1 ; Pasbakhsh P1 ; Kashani IR1 ; Sabbaghziarani F1 ; Omidi A1 ; Zendedel A2 ; Ghasemi S1 ; Dehpour AR3
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Authors Affiliations
  1. 1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Institute of Neuroanatomy, School of Medicine, RWTH Aachen University, Aachen, 52074, Germany
  3. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Iranian Biomedical Journal Published:2016


Abstract

Background: Bone marrow-derived mesenchymal stem cells (BMMSCs) transplantation has been considered as a promising milestone in liver fibrosis treatment. However, low amounts of homing are a major obstacle. We aimed to investigate the role of melatonin pretreatment in BMMSC homing into experimental liver fibrosis. Methods: BMMSCs were obtained, grown, propagated and preconditioned with 5 µM melatonin and analyzed for multipotency and immunophenotypic features at passage three. The cells were labelled with CM-Dil and infused into the rats received the i.p. injection of carbon tetrachloride (CCl4) for five weeks to induce liver fibrosis. Animals were divided into two groups: One group received BMMSCs, whereas the other group received melatonin-pretreated BMMSCs (MT-BMMSCs). After cell injection at 72 h, animals were sacrificed, and the liver tissues were assessed for further evaluations: fibrosis using Masson’s trichrome and hematoxylin and eosin staining and homing using fluorescent microscopy and flow cytometry. Results: BMMSCs and MT-BMMSCs expressed a high level of CD44 but low levels of CD11b, CD45 and CD34 (for all P≤0.05) and were able to differentiate into adipocytes and Schwann cells. CCl4 induction resulted in extensive collagen deposition, tissue disruption and fatty accumulation with no obvious difference between the two groups. There was a significant increase in homing of MT-BMMSCs in both florescent microscopy (P≤0.001) and flow cytometry (P≤0.01) assays, as compared with non-treated BMMSCs. Conclusion: This study indicates the improved homing potential of BMMSCs in pretreatment with melatonin. Therefore, this strategy may represent an applied approach for improving the stem cell therapy of liver fibrosis. © 2016, Pasteur Institute of Iran. All rights reserved.
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