PMID- 10869283
OWN - NLM
STAT- MEDLINE
DCOM- 20000719
LR  - 20220408
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 32
IP  - 1
DP  - 2000 Jul
TI  - Liver from bone marrow in humans.
PG  - 11-6
AB  - It has been shown in animal models that hepatocytes and cholangiocytes can derive 
      from bone marrow cells. We have investigated whether such a process occurs in 
      humans. Archival autopsy and biopsy liver specimens were obtained from 2 female 
      recipients of therapeutic bone marrow transplantations with male donors and from 
      4 male recipients of orthotopic liver transplantations from female donors. 
      Immunohistochemical staining with monoclonal antibody CAM5.2, specific for 
      cytokeratins 8, 18, and 19, gave typical strong staining of hepatocytes, 
      cholangiocytes, and ductular reactions in all tissues, to the exclusion of all 
      nonepithelial cells. Slides were systematically photographed and then restained 
      by fluorescence in situ hybridization (FISH) for X and Y chromosomes. Using 
      morphologic criteria, field-by-field comparison of the fluorescent images with 
      the prior photomicrographs, and persistence of the diaminiobenzidene (DAB) stain 
      through the FISH protease digestion, Y-positive hepatocytes and cholangiocytes 
      could be identified in male control liver tissue and in all study specimens. Cell 
      counts were adjusted based on the number of Y-positive cells in the male control 
      liver to correct for partial sampling of nuclei in the 3-micron thin tissue 
      sections. Adjusted Y-positive hepatocyte and cholangiocyte engraftment ranged 
      from 4% to 43% and from 4% to 38%, respectively, in study specimens, with the 
      peak values being found in a case of fibrosing cholestatic recurrent hepatitis C 
      in one of the liver transplant recipients. We therefore show that in humans, 
      hepatocytes and cholangiocytes can be derived from extrahepatic circulating stem 
      cells, probably of bone marrow origin, and such "transdifferentiation can 
      replenish large numbers of hepatic parenchymal cells.
FAU - Theise, N D
AU  - Theise ND
AD  - Department of Pathology, New York University, School of Medicine, New York, NY 
      10016, USA. Neil.Theise@med.nyu.edu
FAU - Nimmakayalu, M
AU  - Nimmakayalu M
FAU - Gardner, R
AU  - Gardner R
FAU - Illei, P B
AU  - Illei PB
FAU - Morgan, G
AU  - Morgan G
FAU - Teperman, L
AU  - Teperman L
FAU - Henegariu, O
AU  - Henegariu O
FAU - Krause, D S
AU  - Krause DS
LA  - eng
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
SB  - IM
CIN - Hepatology. 2000 Nov;32(5):1181. PMID: 11184476
MH  - Adult
MH  - Bone Marrow Cells/*physiology
MH  - Bone Marrow Transplantation
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Liver/*cytology
MH  - Liver Transplantation
MH  - Male
MH  - Middle Aged
MH  - Stem Cells/*physiology
EDAT- 2000/06/28 11:00
MHDA- 2000/07/25 11:00
CRDT- 2000/06/28 11:00
PHST- 2000/06/28 11:00 [pubmed]
PHST- 2000/07/25 11:00 [medline]
PHST- 2000/06/28 11:00 [entrez]
AID - S0270913900830116 [pii]
AID - 10.1053/jhep.2000.9124 [doi]
PST - ppublish
SO  - Hepatology. 2000 Jul;32(1):11-6. doi: 10.1053/jhep.2000.9124.