Transplantation of basic fibroblast growth factor-pretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice.
Adipose tissue-derived stromal cells (ADSC) potentially differentiate into various cell types similar to bone marrow-derived mesenchymal stromal cells (BMSC). Unlike BMSC, ADSC can be harvested easily and repeatedly. However, the advantages of ADSC for cell transplantation in liver disease remain unclear. To investigate this, we developed a novel culture system for ADSC, as well as effective methods for transplantation of ADSC into mice liver. ADSC were isolated from subcutaneous adipose tissues of male C57BL6/J mice and cultured on plastic dishes with or without basic fibroblast growth factor (bFGF). In the in vivo study, ADSC isolated from green fluorescent protein-transgenic mice were transplanted into carbon tetrachloride-injured C57BL6/J mice liver. bFGF-treated ADSC expressed several liver-specific marker genes and demonstrated liver-related functions such as albumin secretion, glycogen synthesis, urea production, and low-density lipoprotein uptake. Importantly, pretreatment of ADSC with bFGF for 1 wk enhanced the repopulation rate of ADSC in mice liver, attenuated liver fibrosis, and restored normal serum alanine aminotransferase and albumin levels. The results indicate that basic FGF facilitates transdifferentiation of ADSC into hepatic lineage cells in vitro and that transplantation of bFGF-pretreated ADSC reduced hepatic fibrosis in mice. ADSC are a potentially valuable source of cells for transplantation therapy.
Kamada
Yoshihiro
Y
Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan.
Yoshida
Yuichi
Y
Saji
Yukiko
Y
Fukushima
Juichi
J
Tamura
Shinji
S
Kiso
Shinichi
S
Hayashi
Norio
N
D000418:Albumins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride; D018929:Cell Culture Techniques; D019070:Cell Lineage / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects*; D017690:Cell Transplantation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000601:surgery*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors
D000418:Albumins; D053538:Keratin-18; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; C485184:enhanced green fluorescent protein; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D002251:Carbon Tetrachloride