Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Stem Cells. Dec 26, 2011; 3(12): 113-121
Published online Dec 26, 2011. doi: 10.4252/wjsc.v3.i12.113
Hepatogenic differentiation of mesenchymal stem cells induced by insulin like growth factor-I
Maryam Ayatollahi, Masoud Soleimani, Seyed Ziaadin Tabei, Maryam Kabir Salmani
Maryam Ayatollahi, Transplant Research Center, Nemazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
Masoud Soleimani, Hematology Department, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, Iran
Seyed Ziaadin Tabei, Pathology Department, Shiraz University of Medical Sciences, Shiraz, Iran
Maryam Kabir Salmani, Molecular Genetics Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
Author contributions: Ayatollahi M helped in the study design, preparation of the technical works and drafting the article; Soleimani M, Kabir Salmani M and Tabei SZ helped in the study design and technical assistance.
Supported by A grant from Stem Cell Organization: www.stemcell.ir
Correspondence to: Maryam Ayatollahi, PhD, Assistant Professor, Transplant Research Center, Nemazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. ayatollmb@yahoo.com
Telephone: +98-711-6474331 Fax: +98-711-6474331
Received: August 6, 2011
Revised: October 30, 2011
Accepted: November 7, 2011
Published online: December 26, 2011
Abstract

AIM: To improve hepatic differentiation of human mesenchymal stem cell (MSC) using insulin growth factor 1 (IGF-I), which has important role in liver development, hepatocyte differentiation and function.

METHODS: Bone marrow of healthy donors was aspirated from the iliac crest. The adherent cells expanded rapidly and were maintained with periodic passages until a relatively homogeneous population was established. The identification of these cells was carried out by immunophenotype analysis and differentiation potential into osteocytes and adipocytes. To effectively induce hepatic differentiation, we designed a protocol based on a combination of IGF-I and liver specific factors (hepatocyte growth factor, oncostatin M and dexamethasone). Morphological features, hepatic functions and cytological staining were assessed to evaluate transdifferentiation of human marrow-derived MSCs.

RESULTS: Flow cytometric analysis and the differentiation potential into osteoblasts and adipocytes showed that more than 90% of human MSCs which were isolated and expanded were positive by specific markers and functional tests. Morphological assessment and evaluation of glycogen storage, albumin and α-feto protein expression, as well as albumin and urea secretion revealed a statistically significant difference between the experimental groups and control.

CONCLUSION: In vitro differentiated MSCs using IGF-I were able to display advanced liver metabolic functions, supporting the possibility of developing them as potential alternatives to primary hepatocytes.

Keywords: Mesenchymal stem cell; Differentiation; Hepatocyte; Insulin-like growth factor 1; Human