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Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-05-1338.
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Blood, 15 May 2003, Vol. 101, No. 10, pp. 4201-4208
TRANSPLANTATION
Albumin-expressing hepatocyte-like cells develop in the livers of
immune-deficient mice that received transplants of highly purified
human hematopoietic stem cells
Xiuli Wang,
Shundi Ge,
George McNamara,
Qian-Lin Hao,
Gay M. Crooks, and
Jan A. Nolta
From the Division of Research Immunology/Bone
Marrow Transplantation, Childrens Hospital Los Angeles (CHLA),
Los Angeles, CA; the Department of Pediatrics, University of Southern
California School of Medicine, Los Angeles, CA; and the Childrens
Hospital Los Angeles Research Institute, Congressman Dixon Cellular
Imaging Core, Los Angeles, CA.
Rodent bone marrow cells can contribute to liver. If these
findings are applicable to humans, marrow stem cells could
theoretically be harvested from a patient and used to repair
his/her damaged liver. To explore this potential,
CD34+ or highly purified
CD34+CD38 CD7 human
hematopoietic stem cells from umbilical cord blood and bone marrow were
transplanted into immunodeficient mice. One month after
transplantation, carbon tetrachloride (CCl4) was
administered into the mice to induce liver damage and hepatocyte
proliferation. Mice were analyzed in comparison with
CCl4-injured mice that did not receive transplants and
noninjured controls that received transplants with the same stem cell
populations, one month after liver damage. Human-specific albumin mRNA
and protein were expressed in the mouse liver and human albumin was
detected in the serum of mice that had received
CCl4 injury. Human alpha-fetoprotein was never
expressed, but in some mice, human cytokeratin 19 was expressed, which
may indicate bile duct development in addition to the albumin-secreting
hepatocyte-like cells. Human albumin was not expressed in the starting
stem cell populations in injured mice that did not receive transplants
nor in noninjured mice that had received transplants of human stem
cells. Human albumin expression was detected only in
CCl4-treated mice that received transplants of human stem
cells, and recovery was increased by administration of human hepatocyte
growth factor 48 hours after the CCl4-mediated liver injury. Our studies provide evidence that human
"hematopoietic" stem/progenitor cell populations have the capacity
to respond to the injured liver microenvironment by inducing albumin expression.
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