PMID- 9862853
OWN - NLM
STAT- MEDLINE
DCOM- 19990203
LR  - 20121115
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 29
IP  - 1
DP  - 1999 Jan
TI  - Restoration of serum albumin levels in nagase analbuminemic rats by hepatocyte 
      transplantation.
PG  - 75-81
AB  - Recently, we described a new strategy for hepatocyte transplantation, using 
      retrorsine/partial hepatectomy (PH) in a DPPIV- mutant Fischer rat model. 
      Treatment of rats with retrorsine, a pyrrolizidine alkaloid, blocks endogenous 
      hepatocytes from proliferating, so that after exposure to this agent coupled with 
      PH and hepatocyte transplantation, transplanted hepatocytes selectively 
      repopulate the liver. In the present study, we determined whether this method of 
      cell transplantation can restore biosynthetic and physiological function in the 
      liver by transplanting normal hepatocytes into rats genetically deficient in 
      albumin synthesis, the Nagase analbuminic rat (NAR). After hepatocyte 
      transplantation, albumin mRNA and protein were identified in the liver by in situ 
      hybridization and immunohistochemistry, respectively, and serum albumin levels 
      were determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis 
      (SDS-PAGE), Western blot, and enzyme-linked immunosorbent assay (ELISA) methods. 
      At 1 month posttransplantation, large clusters of cells expressing albumin mRNA 
      and protein were identified in the liver, representing approximately 50% of 
      hepatocytes for albumin mRNA and approximately 61% for protein. At 2 months' 
      posttransplantation, cells expressing albumin mRNA represented approximately 77% 
      of hepatocyte mass, and cells expressing albumin protein represented 
      approximately 81% of total hepatocyte mass. Hepatocyte-transplanted NAR also 
      exhibited normal or near-normal serum albumin levels (3.0 +/- 0.2 g/dL). High 
      levels of serum albumin were sustained for the 2-month duration of experiments. 
      These results demonstrate the ability of this protocol for hepatocyte 
      transplantation to restore a major biosynthetic and physiological function of the 
      liver, and suggest its potential use as a method to treat genetic-based or 
      acquired liver diseases.
FAU - Oren, R
AU  - Oren R
AD  - The Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 
      Bronx 10461, NY, USA.
FAU - Dabeva, M D
AU  - Dabeva MD
FAU - Petkov, P M
AU  - Petkov PM
FAU - Hurston, E
AU  - Hurston E
FAU - Laconi, E
AU  - Laconi E
FAU - Shafritz, D A
AU  - Shafritz DA
LA  - eng
GR  - P30 DK41296/DK/NIDDK NIH HHS/United States
GR  - R01 DK17609/DK/NIDDK NIH HHS/United States
GR  - R01 DK50636/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Pyrrolizidine Alkaloids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serum Albumin)
RN  - EC 3.2.1.52 (Acetylglucosaminidase)
RN  - XJ86XWL8IY (retrorsine)
SB  - IM
MH  - Acetylglucosaminidase/*deficiency
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Cell Separation
MH  - *Cell Transplantation
MH  - Diet
MH  - In Situ Hybridization
MH  - Liver/*metabolism/pathology
MH  - Male
MH  - Pyrrolizidine Alkaloids/pharmacology
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Sprague-Dawley
MH  - Serum Albumin/biosynthesis/deficiency/*metabolism
EDAT- 1998/12/24 00:00
MHDA- 1998/12/24 00:01
CRDT- 1998/12/24 00:00
PHST- 1998/12/24 00:00 [pubmed]
PHST- 1998/12/24 00:01 [medline]
PHST- 1998/12/24 00:00 [entrez]
AID - S0270913999000129 [pii]
AID - 10.1002/hep.510290147 [doi]
PST - ppublish
SO  - Hepatology. 1999 Jan;29(1):75-81. doi: 10.1002/hep.510290147.