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Mouse white adipose tissue‐derived mesenchymal stem cells gain pericentral and periportal hepatocyte features after differentiation in vitro , which are preserved in vivo after hepatic transplantation
Author(s) -
Winkler S.,
Hempel M.,
Brückner S.,
Mallek F.,
Weise A.,
Liehr T.,
Tautenhahn H.M.,
Bartels M.,
Christ B.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12560
Subject(s) - mesenchymal stem cell , adipose tissue , biology , stem cell , hepatocyte , transplantation , cellular differentiation , microbiology and biotechnology , in vitro , medicine , endocrinology , biochemistry , gene
Aim Mesenchymal stem cells may differentiate into hepatocyte‐like cells in vitro and in vivo . Therefore, they are considered a novel cell resource for the treatment of various liver diseases. Here, the aim was to demonstrate that mesenchymal stem cells may adopt both perivenous and periportal hepatocyte‐specific functions in vitro and in vivo . Methods Adipose tissue‐derived mesenchymal stem cells were isolated from immunodeficient C57 BL /6 (B6.129S6‐ Rag2 tm1Fwa Prf1 tm1Clrk ) mice and differentiated into the hepatocytic phenotype by applying a simple protocol. Their physiological and metabolic functions were analysed in vitro and after hepatic transplantation in vivo . Results Mesenchymal stem cells changed their morphology from a fibroblastoid into shapes of osteocytes, chondrocytes, adipocytes and hepatocytes. Typical for mesenchymal stem cells, hematopoietic marker genes were not expressed. CD 90, which is not expressed on mature hepatocytes, decreased significantly after hepatocytic differentiation. Markers indicative for liver development like hepatic nuclear factor 4 alpha, or for perivenous hepatocyte specification like cytochrome P450 subtype 3a11, and CD 26 were significantly elevated. Periportal hepatocyte‐specific markers like carbamoylphosphate synthetase 1, the entry enzyme of the urea cycle, were up‐regulated. Consequently, cytochrome P450 enzyme activity and urea synthesis increased significantly to values comparable to cultured primary hepatocytes. Both perivenous and periportal qualities were preserved after hepatic transplantation and integration into the host parenchyma. Conclusions Adult mesenchymal stem cells from adipose tissue differentiated into hepatocyte‐like cells featuring both periportal and perivenous functions. Hence, they are promising candidates for the treatment of region‐specific liver cell damage and may support organ regeneration in acute and chronic liver diseases.