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
ABSTRACT
Wharton's Jelly-Mesenchymal Stem Cells [WJ-MSCs] are pluripotent cells with differentiation capability into most cell lineages. The aim of the current work was to examine the role of Retinoic Acid [RA] in differentiation process of these cells into hepatocyte-like cells and determine the morphological and functional patterns. Human WJ-MSCs were extracted, cultured and expanded; after approximately 95% of confluence, the cells were treated with hepatogenic media containing RA. The cells were subsequently analyzed for morphological changes, glycogen storage, albumin production, and specific gene expression. WJ-MSCs expressed high levels of CD90 [93.6%] and CD105 [90.7%], but low levels of CD34 [0.3%] and CD45 [0.8%]. Albumin production had significant difference in the two groups [p=0.05]. The data showed specific characteristics in favor of considering the differentiated cells as hepatocyte-like cells such as obtaining morphologic, functional, and alphaFP and HNF1-alpha expression patterns which in turn were higher in cells exposed to RA. Based on the data of present study, RA is an effective molecule in inducing differentiation of WJ-MSCs into hepatocyte-like cells; therefore, it may be considered as a promising factor for targeting therapy of liver disorders