Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells.
OBJECTIVE
To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells (ADSC) and bone marrow-derived mesenchymal stem cells (BMSC) in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC.


METHODS
BMSCs were obtained from patients undergoing total hip arthroplasty and ADSC from human adipose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver development using a 2-step protocol with sequential addition of growth factors, cytokines and hormones. Hepatic differentiation was RT-PCR-assessed and liver-marker genes were immunohistochemically analysed.


RESULTS
BMSC and ADSC exhibited a fibroblastic morphology that changed to a polygonal shape when cells differentiated. Expression of stem cell marker Thy1 decreased in differentiated ADSC and BMSC. However, the expression of the hepatic markers, albumin and CYPs increased to a similar extent in differentiated BMSC and ADSC. Hepatic gene activation could be attributed to increased liver-enriched transcription factors (C/EBPbeta and HNF4alpha), as demonstrated by adenoviral expression vectors.


CONCLUSIONS
Mesenchymal stem cells can be induced to hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic differentiation potential to BMSC, but a longer culture period and higher proliferation capacity. Therefore, adipose tissue may be an ideal source of large amounts of autologous stem cells, and may become an alternative for hepatocyte regeneration, liver cell transplantation or preclinical drug testing.
Taléns-Visconti
Raquel
R
Unidad de Hepatologia Experimental, Centro de Investigacion. Hospital Universitario La Fe, Avda Campanar 21, E-46009-Valencia, Spain.
Bonora
Ana
A
Jover
Ramiro
R
Mirabet
Vicente
V
Carbonell
Francisco
F
Castell
José-Vicente
JV
Gómez-Lechón
María José
MJ
D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D000328:Adult; D000368:Aged; D000418:Albumins / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D010641:Phenotype; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D000418:Albumins; D022782:CCAAT-Enhancer-Binding Protein-beta; D051557:Hepatocyte Nuclear Factor 4; D018800:Thy-1 Antigens; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human