Human bone marrow mesenchymal stem cell‐derived hepatocytes express tissue inhibitor of metalloproteinases 4 and follistatin. (17th February 2015)

• Record Type: Journal Article
• Authors: Xin, Jiaojiao; Ding, Wenchao; Hao, Shaorui; Jiang, Longyan; Zhou, Qian; Wu, Tianzhou; Shi, Dongyan; Cao, Hongcui; Li, Lanjuan; Li, Jun
• Is Part Of: Liver international. Volume 35:Number 10(2015:Oct.)
• Page Start: 2301
• Page End: 2310
• Publication Date: 2015-02-17
• Subjects: Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.12797
• Languages: English
• ISSNs: 1478-3223

Abstract

<abstract abstract-type="main" id="liv12797-abs-0001"> <title>Abstract</title> <sec id="liv12797-sec-0001" sec-type="section"> <title>Background & Aims</title> <p>Human bone marrow mesenchymal stem cell (hBMSC) transplantation is expected to become an alternative regenerative technique for liver diseases. However, the mechanism by which hBMSCs differentiate into hepatocytes is still unclear. The aim of this study was to establish the specific characteristics of hBMSC‐derived hepatocytes (hBMSC‐Heps) for future clinical applications.</p> </sec> <sec id="liv12797-sec-0002" sec-type="section"> <title>Methods</title> <p>Potential hBMSC‐Hep biomarkers were screened using cytokine arrays. Significant biomarkers were then validated by enzyme‐linked immunosorbent assay (ELISA) <italic>in vitro</italic> and in an <italic>in vivo</italic> xenotransplantation model in fulminant hepatic failure (FHF) pigs.</p> </sec> <sec id="liv12797-sec-0003" sec-type="section"> <title>Results</title> <p>After 20 days of differentiation, the expression levels of tissue inhibitor of metalloproteinases 4 (TIMP‐4) and follistatin (FST) in functional hBMSC‐Heps were significantly increased, whereas those of activin A, osteoprotegerin and platelet‐derived growth factor α polypeptide (PDGF‐A) were significantly decreased. The high levels of TIMP‐4 and FST were validated by ELISA in hBMSC‐Heps grown in differentiation medium. The <italic>in vivo</italic> xenotransplantation model in FHF pigs showed that the serum levels of TIMP‐4 and FST were significantly increased 6 h after hBMSC transplantation and reached their highest levels at 24 and 48 h, respectively, after hBMSC transplantation. Immunohistochemistry confirmed that TIMP‐4 and FST were expressed in cultured hBMSC‐Heps and in implanted hBMSC‐Heps in pig livers.</p> </sec> <sec id="liv12797-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The transdifferentiation of hBMSCs into hepatocytes is associated with the expression of TIMP‐4 and FST. TIMP‐4 and FST represent potential novel biomarkers for the characterisation of hBMSC‐Heps and may be useful for future clinical applications.</p> </sec> </abstract>