Enhanced hepatic differentiation of mesenchymal stem cells after pretreatment with injured liver tissue

Liver failure represents a serious challenge for cell based therapies. Mesenchymal stem cells (MSCs) possess potential for regeneration of fibrotic liver; however, there is a dire need to improve their hepatic differentiation. This study examines a pretreatment strategy to augment the differentiatio...

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Bibliographic Details
Published in:Differentiation (London) 2011, Vol.81 (1), p.42-48
Main Authors: Mohsin, Sadia, Shams, Sulaiman, Ali Nasir, Ghazanfar, Khan, Mohsin, Javaid Awan, Sana, Khan, Shaheen N., Riazuddin, Sheikh
Format: Article
Language:English
Subjects:
Albumins - genetics
Animals
Carbon Tetrachloride
Cell Differentiation
Cells, Cultured
Cellular therapy
Chemical and Drug Induced Liver Injury
Flow Cytometry
Gene Products, tat - genetics
Hepatic differentiation
Hepatocyte Nuclear Factor 1-alpha - genetics
Hepatocytes - cytology
Keratins - genetics
Liver - cytology
Liver Cirrhosis - therapy
Liver fibrosis
Mesenchymal Stem Cell Transplantation - veterinary
Mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - physiology
Mice
Mice, Inbred C57BL
Receptors, Cell Surface - immunology
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Summary:Liver failure represents a serious challenge for cell based therapies. Mesenchymal stem cells (MSCs) possess potential for regeneration of fibrotic liver; however, there is a dire need to improve their hepatic differentiation. This study examines a pretreatment strategy to augment the differentiation potential of MSCs towards hepatic lineage. MSCs were isolated from C57BL/6 wild type mice and were characterized by flow cytometry for CD44 (92.4%), CD90 (96.6%), CD105 (94.7%), CD45 (0.8%) and CD34 (1.4%) markers. To improve the differentiation potential of MSCs towards hepatic lineage, cells were pretreated with injured liver tissue in an in-vitro model, which resulted in high expression of albumin, cytokeratin 8, 18, TAT and HNF1α as compared to untreated MSCs. The efficacy of pretreated MSCs was evaluated by preparing in-vivo mouse model with liver fibrosis by intraperitoneal administration of CCl 4. Pretreated MSCs were transplanted in the left lateral lobe of mice with liver fibrosis and showed enhanced localization and differentiation abilities after 1 month. The expression for cytokeratin 8, 18, albumin and Bcl-xl was up-regulated and that of HGF, Bax and Caspase- 3 was down-regulated in animals transplanted with pretreated MSCs. Sirus red staining also confirmed a significant reduction in the fibrotic area in liver tissue transplanted with pretreated MSCs as compared to untreated MSCs and was concomitant with improved serum levels of bilirubin and alkaline phosphatase (ALP). Therefore, it was concluded that pretreatment with injured liver tissue augment homing and hepatic differentiation abilities of MSCs and provides an improved procedure for the treatment of liver fibrosis.
ISSN:0301-4681
1432-0436
DOI:10.1016/j.diff.2010.08.005