|
|
Blood, 15 October 2004, Vol. 104, No. 8, pp. 2582-2590.
Prepublished online as a Blood First Edition Paper on July 1, 2004; DOI 10.1182/blood-2004-01-0259.
 Previous Article | Next Article 
Submitted January 22, 2004
Accepted June 11, 2004
Formation of Human Hepatocytes by Human Hematopoietic Stem Cells in Sheep
Graca Almeida-Porada*, Christopher D Porada, Jason Chamberlain, Ali Torabi, and Esmail D Zanjani
Department of Animal Biotechnology & Department of Medicine, University of Nevada, Reno, NV, USA
* Corresponding author; email: galmeida{at}cabnr.unr.edu.
We took advantage of the proliferative and permissive environment of the developing pre-immune fetus to develop a non-injury large animal model in sheep, in which transplantation of defined populations of human hematopoietic stem cells resulted not only in the establishment of human hematopoiesis, but also led to the formation of significant numbers of long-lasting, functional human liver cells, with some animals exhibiting levels as high as 20% of donor (human) hepatocytes at 11 months post-transplant. A direct correlation was found between the hepatocytic activity and the phenotype of the transplanted cells, cell dose administered, sources of cells used on a cell-per-cell basis (bone marrow, cord blood, mobilized peripheral blood) and time after transplant. The human hepatocytes generated in this model retained functional properties of normal hepatocytes, constituted hepatic functional units with the presence of human endothelial and biliary duct cells, and secreted human albumin that was detected in circulation. Transplantation of populations of hematopoietic stem cells can efficiently generate significant numbers of functional hepatic cells in this non-injury large animal model, and thus could be a means of ameliorating/curing genetic diseases in which a deficiency of liver cells or their products threaten the life of the fetus or newborn.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
In utero transplantation: hepatic potential of human CD34+CD45+ progenitors
- Orit Kollet and Tsvee Lapidot
Blood 2004 104: 2207-2208.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
J. A. Fritzell Jr., Q. Mao, S. Gundavarapu, T. Pasquariello, J. M. Aliotta, A. Ayala, J. F. Padbury, and M. E. De Paepe
Fate and Effects of Adult Bone Marrow Cells in Lungs of Normoxic and Hyperoxic Newborn Mice
Am. J. Respir. Cell Mol. Biol.,
May 1, 2009;
40(5):
575 - 587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Khurana and A. Mukhopadhyay
Hematopoietic Progenitors from Early Murine Fetal Liver Possess Hepatic Differentiation Potential
Am. J. Pathol.,
December 1, 2008;
173(6):
1818 - 1827.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Brezillon, D. Kremsdorf, and M. C. Weiss
Cell therapy for the diseased liver: from stem cell biology to novel models for hepatotropic human pathogens
Dis. Model. Mech.,
September 1, 2008;
1(2-3):
113 - 130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L V. di Bonzo, I Ferrero, C Cravanzola, K Mareschi, D Rustichell, E Novo, F Sanavio, S Cannito, E Zamara, M Bertero, et al.
Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential
Gut,
February 1, 2008;
57(2):
223 - 231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Zeng, M.-j. Chen, D. A. Baldwin, Z.-j. Gong, J.-b. Yan, H. Qian, J. Wang, X. Jiang, Z.-r. Ren, D. Sun, et al.
Multiorgan engraftment and differentiation of human cord blood CD34+Lin- cells in goats assessed by gene expression profiling
PNAS,
May 16, 2006;
103(20):
7801 - 7806.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Robert
The science and ethics of making part-human animals in stem cell biology
FASEB J,
May 1, 2006;
20(7):
838 - 845.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Visconti, Y. Ebihara, A. C. LaRue, P. A. Fleming, T. C. McQuinn, M. Masuya, H. Minamiguchi, R. R. Markwald, M. Ogawa, and C. J. Drake
An In Vivo Analysis of Hematopoietic Stem Cell Potential: Hematopoietic Origin of Cardiac Valve Interstitial Cells
Circ. Res.,
March 17, 2006;
98(5):
690 - 696.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Sharma, T. Cantz, R. Richter, K. Eckert, R. Henschler, L. Wilkens, A. Jochheim-Richter, L. Arseniev, and M. Ott
Human Cord Blood Stem Cells Generate Human Cytokeratin 18-Negative Hepatocyte-Like Cells in Injured Mouse Liver
Am. J. Pathol.,
August 1, 2005;
167(2):
555 - 564.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Stadtfeld and T. Graf
Assessing the role of hematopoietic plasticity for endothelial and hepatocyte development by non-invasive lineage tracing
Development,
January 1, 2005;
132(1):
203 - 213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
