Premium
Human bone marrow mesenchymal stem cell‐derived hepatocytes express tissue inhibitor of metalloproteinases 4 and follistatin
Author(s) -
Xin Jiaojiao,
Ding Wenchao,
Hao Shaorui,
Jiang Longyan,
Zhou Qian,
Wu Tianzhou,
Shi Dongyan,
Cao Hongcui,
Li Lanjuan,
Li Jun
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12797
Subject(s) - mesenchymal stem cell , transplantation , bone marrow , follistatin , stem cell , andrology , biology , medicine , immunology , pathology , microbiology and biotechnology
Background & Aims Human bone marrow mesenchymal stem cell ( hBMSC ) transplantation is expected to become an alternative regenerative technique for liver diseases. However, the mechanism by which hBMSC s 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. Methods Potential hBMSC ‐Hep biomarkers were screened using cytokine arrays. Significant biomarkers were then validated by enzyme‐linked immunosorbent assay ( ELISA ) in vitro and in an in vivo xenotransplantation model in fulminant hepatic failure ( FHF ) pigs. Results 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 in vivo 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. Conclusions The transdifferentiation of hBMSC s 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.