Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure.
OBJECTIVE
Multipotential mesenchymal stem cells (MSC), present in many organs and tissues, represent an attractive tool for the establishment of a successful stem cell-based therapy in the field of regeneration medicine. Adipose tissue mesenchymal stem cells (AT-MSC), known as adipose-derived stem cells (ASC) are especially attractive in the context of future clinical applications because of their high accessibility and minimal invasiveness during the procedure to obtain them. The goal of the present study was to induce human ASC into functional hepatocytes in vitro within a very short period of time and to check their therapeutic potential in vivo.


METHODS
In vitro generated ASC-derived hepatocytes were checked for hepatocyte-specific markers and functions. Afterwards, they were transplanted into nude mice with liver injury. Twenty-four hours after transplantation, biochemical parameters were evaluated in blood serum.


RESULTS
We have shown here that ASC can be differentiated into hepatocytes within 13 days and can reach the functional properties of primary human hepatocytes. After transplantation into mice with acute liver failure, ASC-derived hepatocytes can restore such liver functions as ammonia and purine metabolism. Markers of liver injury, alanine aminotransferase, aspartate aminotransferase, as well as ammonia, were decreased after ASC-derived hepatocyte transplantation.


CONCLUSIONS
Our data highlight the properties of ASC as having a special affinity for hepatocyte differentiation in vitro and liver regeneration in vivo. Thus, ASC may be a superior choice for the establishment of a therapy for injured liver.
Banas
Agnieszka
A
Section for Studies on Metastasis, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Teratani
Takumi
T
Yamamoto
Yusuke
Y
Tokuhara
Makoto
M
Takeshita
Fumitaka
F
Osaki
Mitsuhiko
M
Kato
Takashi
T
Okochi
Hitoshi
H
Ochiya
Takahiro
T
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000641:Ammonia / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D008115:Liver Regeneration; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D050151:Subcutaneous Fat / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D014527:Uric Acid / Q000097:blood
D015415:Biomarkers; D014527:Uric Acid; D000641:Ammonia; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase