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Science 14 May 1999:
Vol. 284. no. 5417, pp. 1168 - 1170
DOI: 10.1126/science.284.5417.1168
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Reports

Bone Marrow as a Potential Source of Hepatic Oval Cells

B. E. Petersen, 1* W. C. Bowen, 1 K. D. Patrene, 2 W. M. Mars, 1 A. K. Sullivan, 4dagger N. Murase, 3 S. S. Boggs, 2 J. S. Greenberger, 2 J. P. Goff 2

Bone marrow stem cells develop into hematopoietic and mesenchymal lineages but have not been known to participate in production of hepatocytes, biliary cells, or oval cells during liver regeneration. Cross-sex or cross-strain bone marrow and whole liver transplantation were used to trace the origin of the repopulating liver cells. Transplanted rats were treated with 2-acetylaminofluorene, to block hepatocyte proliferation, and then hepatic injury, to induce oval cell proliferation. Markers for Y chromosome, dipeptidyl peptidase IV enzyme, and L21-6 antigen were used to identify liver cells of bone marrow origin. From these cells, a proportion of the regenerated hepatic cells were shown to be donor-derived. Thus, a stem cell associated with the bone marrow has epithelial cell lineage capability.

1 Department of Pathology,
2 Department of Radiation Oncology,
3 Division of Transplant Pathology, Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
4 Department of Hematology/Oncology, McGill University, Quebec H3A 2T5, Canada.
*   To whom correspondence should be addressed. E-mail: bryon+@pitt.edu

dagger    Present address: Department of Oncology, King Faisal Specialist Hospital and Research Centre, Post Office Box 3354, Riyadh, Kingdom of Saudi Arabia.

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Differentiation of Bone Marrow Stromal Cells Into the Cardiac Phenotype Requires Intercellular Communication With Myocytes.
M. Xu, M. Wani, Y.-S. Dai, J. Wang, M. Yan, A. Ayub, and M. Ashraf (2004)
Circulation 110, 2658-2665
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Formation of human hepatocytes by human hematopoietic stem cells in sheep.
G. Almeida-Porada, C. D. Porada, J. Chamberlain, A. Torabi, and E. D. Zanjani (2004)
Blood 104, 2582-2590
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Adult bone-marrow stem cells and their potential in medicine.
H T Hassan and M El-Sheemy (2004)
J R Soc Med 97, 465-471
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Adult skeletal muscle stem cells differentiate into endothelial lineage and ameliorate renal dysfunction after acute ischemia.
M. Arriero, S. V. Brodsky, O. Gealekman, P. A. Lucas, and M. S. Goligorsky (2004)
Am J Physiol Renal Physiol 287, F621-F627
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Bone Marrow Stromal Cells, Preadipocytes, and Dermal Fibroblasts Promote Epidermal Regeneration in Their Distinctive Fashions.
S. Aoki, S. Toda, T. Ando, and H. Sugihara (2004)
Mol. Biol. Cell 15, 4647-4657
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Functional Recovery of Stroke Rats Induced by Granulocyte Colony-Stimulating Factor-Stimulated Stem Cells.
W.-C. Shyu, S.-Z. Lin, H.-I Yang, Y.-S. Tzeng, C.-Y. Pang, P.-S. Yen, and H. Li (2004)
Circulation 110, 1847-1854
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Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells.
A. Hermann, R. Gastl, S. Liebau, M. O. Popa, J. Fiedler, B. O. Boehm, M. Maisel, H. Lerche, J. Schwarz, R. Brenner, et al. (2004)
J. Cell Sci. 117, 4411-4422
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Neurogenesis of Rhesus adipose stromal cells.
S. K. Kang, L. A. Putnam, J. Ylostalo, I. R. Popescu, J. Dufour, A. Belousov, and B. A. Bunnell (2004)
J. Cell Sci. 117, 4289-4299
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A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential.
G. Kogler, S. Sensken, J. A. Airey, T. Trapp, M. Muschen, N. Feldhahn, S. Liedtke, R. V. Sorg, J. Fischer, C. Rosenbaum, et al. (2004)
J. Exp. Med. 200, 123-135
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In Vivo and In Vitro Characterization of Insulin-Producing Cells Obtained From Murine Bone Marrow.
D.-Q. Tang, L.-Z. Cao, B. R. Burkhardt, C.-Q. Xia, S. A. Litherland, M. A. Atkinson, and L.-J. Yang (2004)
Diabetes 53, 1721-1732
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Plasticity of Bone Marrow-Derived Stem Cells.
J. E. Grove, E. Bruscia, and D. S. Krause (2004)
Stem Cells 22, 487-500
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Bone marrow engraftment in a rodent model of chemical carcinogenesis but no role in the histogenesis of hepatocellular carcinoma.
H Ishikawa, K Nakao, K Matsumoto, D Nishimura, T Ichikawa, K Hamasaki, and K Eguchi (2004)
Gut 53, 884-889
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Artificial Liver Support: Potential to Retard Regeneration?.
E. J. Mullin, M. S. Metcalfe, and G. J. Maddern (2004)
Arch Surg 139, 670-677
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Functional Expression of HGF and HGF Receptor/c-met in Adult Human Mesenchymal Stem Cells Suggests a Role in Cell Mobilization, Tissue Repair, and Wound Healing.
S. Neuss, E. Becher, M. Woltje, L. Tietze, and W. Jahnen-Dechent (2004)
Stem Cells 22, 405-414
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Tubular Chimerism Occurs Regularly in Renal Allografts and Is Not Correlated to Outcome.
M. Mengel, D. Jonigk, M. Marwedel, W. Kleeberger, M. Bredt, O. Bock, U. Lehmann, W. Gwinner, H. Haller, and H. Kreipe (2004)
J. Am. Soc. Nephrol. 15, 978-986
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Epithelial Tissue Chimerism after Human Hematopoietic Cell Transplantation Is a Real Phenomenon.
A. Spyridonidis, A. Schmitt-Graff, T. Tomann, A. Dwenger, M. Follo, D. Behringer, and J. Finke (2004)
Am. J. Pathol. 164, 1147-1155
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Transit-Amplifying Ductular (Oval) Cells and Their Hepatocytic Progeny Are Characterized by a Novel and Distinctive Expression of Delta-Like Protein/Preadipocyte Factor 1/Fetal Antigen 1.
C. H. Jensen, E. I. Jauho, E. Santoni-Rugiu, U. Holmskov, B. Teisner, N. Tygstrup, and H. C. Bisgaard (2004)
Am. J. Pathol. 164, 1347-1359
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Amniotic Membrane as a Carrier for Cultivated Human Corneal Endothelial Cell Transplantation.
Y. Ishino, Y. Sano, T. Nakamura, C. J. Connon, H. Rigby, N. J. Fullwood, and S. Kinoshita (2004)
Invest. Ophthalmol. Vis. Sci. 45, 800-806
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Epidermal cells accelerate the restoration of the blood flow in diabetic ischemic limbs.
C. Jiao, S. Bronner, K. L. N. Mercer, D. D. Sheriff, G. C. Schatteman, and M. Dunnwald (2004)
J. Cell Sci. 117, 1055-1063
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