PMID- 18957046
OWN - NLM
STAT- MEDLINE
DCOM- 20090115
LR  - 20110603
IS  - 1399-3089 (Electronic)
IS  - 0908-665X (Linking)
VI  - 15
IP  - 4
DP  - 2008 Jul-Aug
TI  - Engraftment of human hepatocytes in the livers of rats bearing bone marrow 
      reconstructed with immunodeficient mouse bone marrow cells.
PG  - 235-45
LID - 10.1111/j.1399-3089.2008.00483.x [doi]
AB  - BACKGROUND: Previously, we created, a chimeric mouse (humanized mouse), a severe 
      combined immunodeficiency (SCID) mouse whose liver was >90% repopulated with 
      human (h)-hepatocytes, which are useful for the testing of drug metabolism and 
      toxicity, as well as a hepatitis B virus and hepatitis C virus-susceptible animal 
      model. However, their small body size and small total blood volume limited the 
      utilization for analytical purposes, which led us to develop a method to create a 
      chimeric rat bearing h-hepatocyte-repopulated liver. METHODS: F344 nude rats 
      devoid of T cells were irradiated with X-rays and injected with bone marrow cells 
      (BMCs) from SCID mice (m(SCID)). The rate of replacement with m(SCID)-BMCs was 
      evaluated by two-color flow cytometry analysis of peripheral blood mononuclear 
      cells (PBMCs). After m(SCID)-BMCs repopulated the host bone marrow (BM), the rats 
      were treated with retrorsine, partially hepatectomized (PHx), and transplanted 
      with 5 x 10(6) h-hepatocytes isolated from the chimeric mice. h-Albumin (h-Alb) 
      concentrations in the host blood and the expression levels of protein and mRNA of 
      hepatocyte differentiation markers in the h-hepatocytes were evaluated by ELISA, 
      immunostaining, and reverse transcription-PCR, respectively. RESULTS: The 
      m(SCID)-BMCs successfully repopulated the rats, the percentage of mouse cells 
      reaching 94% among host (r(nudeF344)) PBMCs at 4 weeks after m-BMC 
      transplantation. h-Hepatocytes isolated from the chimeric mice were transplanted 
      to the liver of the m(SCID)-BMC-repopulated rats. The engrafted h-hepatocytes 
      expressed h-Alb and h-cytochrome P450 (CYP) subtypes and survived showing normal 
      phenotypes until at least 3 weeks post-h-hepatocytes transplantation (h-HPCT). 
      However, the blood concentrations of h-Alb declined at 4 weeks post-HPCT, 
      concomitant with the emergence of both r(nudeF344)- and m(SCID)-macrophages, 
      suggesting the rejection of h-hepatocytes due to the activation of macrophages. 
      CONCLUSION: We developed a novel method to create a rat that bears the liver 
      engrafted with h-hepatocytes, utilizing a rat with the BM composed of 
      m(SCID)-BMCs as a host. This h-hepatocyte-bearing rat will be a valuable model 
      for studying the immunologic mechanisms involved in xenogeneic transplantation 
      and for generating rats with higher rates of repopulation with h-hepatocytes.
FAU - Igarashi, Yuka
AU  - Igarashi Y
AD  - Department of Surgery, Division of Frontier Medical Science, Graduate School of 
      Biomedical Sciences, Hiroshima University, Higashi-Hiroshima, Japan.
FAU - Tateno, Chise
AU  - Tateno C
FAU - Tanaka, Yuka
AU  - Tanaka Y
FAU - Tachibana, Asato
AU  - Tachibana A
FAU - Utoh, Rie
AU  - Utoh R
FAU - Kataoka, Miho
AU  - Kataoka M
FAU - Ohdan, Hideki
AU  - Ohdan H
FAU - Asahara, Toshimasa
AU  - Asahara T
FAU - Yoshizato, Katsutoshi
AU  - Yoshizato K
LA  - eng
PT  - Journal Article
PL  - Denmark
TA  - Xenotransplantation
JT  - Xenotransplantation
JID - 9438793
RN  - 0 (DNA Primers)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow Transplantation/immunology
MH  - DNA Primers/genetics
MH  - Gene Expression Profiling
MH  - Graft Survival
MH  - Hepatocytes/immunology/metabolism/*transplantation
MH  - Humans
MH  - Macrophage Activation
MH  - Mice
MH  - Mice, SCID
MH  - RNA/genetics/metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Nude
MH  - Transplantation Chimera
MH  - Transplantation, Heterologous
EDAT- 2008/10/30 09:00
MHDA- 2009/01/16 09:00
CRDT- 2008/10/30 09:00
PHST- 2008/10/30 09:00 [pubmed]
PHST- 2009/01/16 09:00 [medline]
PHST- 2008/10/30 09:00 [entrez]
AID - XEN483 [pii]
AID - 10.1111/j.1399-3089.2008.00483.x [doi]
PST - ppublish
SO  - Xenotransplantation. 2008 Jul-Aug;15(4):235-45. doi: 
      10.1111/j.1399-3089.2008.00483.x.