PMID- 15817682
OWN - NLM
STAT- MEDLINE
DCOM- 20050818
LR  - 20220317
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 106
IP  - 2
DP  - 2005 Jul 15
TI  - Human mesenchymal stem cells xenografted directly to rat liver are differentiated 
      into human hepatocytes without fusion.
PG  - 756-63
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.
FAU - Sato, Yasushi
AU  - Sato Y
AD  - Fourth Department of Internal Medicine, Sapporo Medical University, School of 
      Medicine, Sapporo, 060-8543, Japan.
FAU - Araki, Hironobu
AU  - Araki H
FAU - Kato, Junji
AU  - Kato J
FAU - Nakamura, Kiminori
AU  - Nakamura K
FAU - Kawano, Yutaka
AU  - Kawano Y
FAU - Kobune, Masayoshi
AU  - Kobune M
FAU - Sato, Tsutomu
AU  - Sato T
FAU - Miyanishi, Koji
AU  - Miyanishi K
FAU - Takayama, Tetsuji
AU  - Takayama T
FAU - Takahashi, Minoru
AU  - Takahashi M
FAU - Takimoto, Rishu
AU  - Takimoto R
FAU - Iyama, Satoshi
AU  - Iyama S
FAU - Matsunaga, Takuya
AU  - Matsunaga T
FAU - Ohtani, Seiji
AU  - Ohtani S
FAU - Matsuura, Akihiro
AU  - Matsuura A
FAU - Hamada, Hirofumi
AU  - Hamada H
FAU - Niitsu, Yoshiro
AU  - Niitsu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050407
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Albumins)
RN  - 0 (Antigens, CD34)
RN  - 0 (Asialoglycoprotein Receptor)
RN  - 0 (RNA, Messenger)
RN  - 0 (alpha-Fetoproteins)
RN  - 68238-35-7 (Keratins)
SB  - IM
MH  - Albumins/genetics/metabolism
MH  - Animals
MH  - Antigens, CD34/metabolism
MH  - Asialoglycoprotein Receptor/metabolism
MH  - Cell Count
MH  - Cell Differentiation
MH  - Female
MH  - Gene Expression
MH  - Hepatocytes/*cytology/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Keratins/metabolism
MH  - Liver/*cytology/metabolism/*surgery
MH  - Membrane Fusion
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transplantation, Heterologous
MH  - alpha-Fetoproteins/genetics/metabolism
EDAT- 2005/04/09 09:00
MHDA- 2005/08/19 09:00
CRDT- 2005/04/09 09:00
PHST- 2005/04/09 09:00 [pubmed]
PHST- 2005/08/19 09:00 [medline]
PHST- 2005/04/09 09:00 [entrez]
AID - S0006-4971(20)53307-7 [pii]
AID - 10.1182/blood-2005-02-0572 [doi]
PST - ppublish
SO  - Blood. 2005 Jul 15;106(2):756-63. doi: 10.1182/blood-2005-02-0572. Epub 2005 Apr 
      7.