title: Melatonin Pretreatment Enhances the Homing of Bone Marrow-derived Mesenchymal Stem Cells Following Transplantation in a Rat Model of Liver Fibrosis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Keywan
authors.initials: K
authors.lastname: Mortezaee
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Parichehr
authors.initials: P
authors.lastname: Pasbakhsh
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Iraj
authors.initials: I
authors.lastname: Ragerdi Kashani
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sabbaghziarani
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ameneh
authors.initials: A
authors.lastname: Omidi
authors.affiliation: Institute of Neuroanatomy, School of Medicine, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Adib
authors.initials: A
authors.lastname: Zendedel
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Soudabeh
authors.initials: S
authors.lastname: Ghasemi
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology; D039481:CD11b Antigen / Q000096:biosynthesis; D002251:Carbon Tetrachloride / Q000633:toxicity; D002465:Cell Movement / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology*
chemical_list: D018952:Antigens, CD34; D039481:CD11b Antigen; D018960:Hyaluronan Receptors; D002251:Carbon Tetrachloride; D017493:Leukocyte Common Antigens; C516771:Ptprc protein, rat; D008550:Melatonin
keywords: Bone marrow; Melatonin; Mesenchymal stem cells