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

• Published in: Iranian biomedical journal 2016-10, Vol.20 (4), p.207-216
• Main Authors: Mortezaee, Keywan, Pasbakhsh, Parichehr, Ragerdi Kashani, Iraj, Sabbaghziarani, Fatemeh, Omidi, Ameneh, Zendedel, Adib, Ghasemi, Soudabeh, Dehpour, Ahmad Reza
• Format: Article
• Language: English
• Subjects: Adipocytes - cytology; Adipogenesis - drug effects; Animals; Antigens, CD34 - biosynthesis; Bone marrow; Bone Marrow Cells - cytology; Carbon Tetrachloride - toxicity; CD11b Antigen - biosynthesis; Cell Movement - drug effects; Cell Transdifferentiation - drug effects; Cell- and Tissue-Based Therapy - methods; Cells, Cultured; Full Length; Growth factors; Hyaluronan Receptors - biosynthesis; Ischemia; Kinases; Leukocyte Common Antigens - biosynthesis; Liver - pathology; Liver Cirrhosis - chemically induced; Liver Cirrhosis - pathology; Liver Cirrhosis - therapy; Male; Melatonin; Melatonin - pharmacology; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - cytology; Rats; Rats, Sprague-Dawley; Schwann Cells - cytology; Stem cells
• ISSN: 1028-852X; 2008-823X
• DOI: 10.7508/ibj.2016.04.004

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. 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. 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. 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.