TY - JOUR
T1 - Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion
AU - Sato, Yasushi
AU - Araki, Hironobu
AU - Kato, Junji
AU - Nakamura, Kiminori
AU - Kawano, Yutaka
AU - Kobune, Masayoshi
AU - Sato, Tsutomu
AU - Miyanishi, Koji
AU - Takayama, Tetsuji
AU - Takahashi, Minoru
AU - Takimoto, Rishu
AU - Iyama, Satoshi
AU - Matsunaga, Takuya
AU - Ohtani, Seiji
AU - Matsuura, Akihiro
AU - Hamada, Hirofumi
AU - Niitsu, Yoshiro
PY - 2005/7/15
Y1 - 2005/7/15
N2 - Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- cells and examined them by directly xenografting to allylalcohol (AA)-treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers.
AB - Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- cells and examined them by directly xenografting to allylalcohol (AA)-treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers.
UR - http://www.scopus.com/inward/record.url?scp=22144460191&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22144460191&partnerID=8YFLogxK
U2 - 10.1182/blood-2005-02-0572
DO - 10.1182/blood-2005-02-0572
M3 - Article
C2 - 15817682
AN - SCOPUS:22144460191
VL - 106
SP - 756
EP - 763
JO - Blood
JF - Blood
SN - 0006-4971
IS - 2
ER -