| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Departments of Molecular and Medical Genetics*and Pediatrics,Oregon Health and Sciences University, Portland, Oregon; Stem Cells Incorporated,Palo Alto, California; and the Department of Pathology,Texas Children’s Hospital, Houston, Texas
Recent work has convincingly demonstrated that adult bone marrow contains cells capable of differentiating into liver epithelial cells in vivo. However, the frequency and time course with which fully functional hepatocytes emerge after bone marrow transplantation remained controversial. Here, we used the fumarylacetoacetate hydrolase knockout mouse to determine the kinetics of hepatocyte replacement after complete hematopoietic reconstitution. Single donor-derived hepatocytes were first detected 7 weeks after lethal irradiation and bone marrow transplantation. Liver disease was not required for this transdifferentiation. In the presence of selective pressure the single cells evolved into hepatocyte nodules by 11 weeks after transplantation and resulted in >30% overall liver repopulation by 22 weeks. The frequency with which hepatocytes were produced was between 10-4 and 10-6, resulting in only 50 to 500 repopulation events per liver. Hepatic engraftment was not observed without previous hematopoietic reconstitution even in the presence of liver injury. In addition, significant liver repopulation was completely dependent on hepatocyte growth selection. We conclude that hepatocyte replacement by bone marrow cells is a slow and rare event. Significant improvements in the efficiency of this process will be needed before clinical success can be expected.
Related articles in Am J Pathol:
This article has been cited by other articles:
 |
|
 |
|
  D P J Kavanagh, L E Durant, H A Crosby, P F Lalor, J Frampton, D H Adams, and N Kalia Haematopoietic stem cell recruitment to injured murine liver sinusoids depends on {alpha}4{beta}1 integrin/VCAM-1 interactions Gut, January 1, 2010; 59(01): 79 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Watanabe, A. Masamune, K. Kikuta, M. Hirota, K. Kume, K. Satoh, and T. Shimosegawa Bone marrow contributes to the population of pancreatic stellate cells in mice Am J Physiol Gastrointest Liver Physiol, December 1, 2009; 297(6): G1138 - G1146. [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]
|
|
|
|
 |
|
 J. Mori, Y. Ishihara, K. Matsuo, H. Nakajima, N. Terada, K. Kosaka, Z. Kizaki, and T. Sugimoto Hematopoietic Contribution to Skeletal Muscle Regeneration in Acid {alpha}-Glucosidase Knockout Mice J. Histochem. Cytochem., September 1, 2008; 56(9): 811 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kubota, J. Soeda, R. Misawa, M. Mihara, S. Miwa, H. Ise, M. Takahashi, and S. Miyagawa Bone marrow-derived cells fuse with hepatic oval cells but are not involved in hepatic tumorigenesis in the choline-deficient ethionine-supplemented diet rat model Carcinogenesis, February 1, 2008; 29(2): 448 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Fujino, H. Hiramatsu, A. Tsuchiya, A. Niwa, H. Noma, M. Shiota, K. Umeda, M. Yoshimoto, M. Ito, T. Heike, et al. Human cord blood CD34+ cells develop into hepatocytes in the livers of NOD/SCID/{gamma}cnull mice through cell fusion FASEB J, November 1, 2007; 21(13): 3499 - 3510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Mouiseddine, S Francois, A Semont, A Sache, B Allenet, N Mathieu, J Frick, D Thierry, and A Chapel Human mesenchymal stem cells home specifically to radiation-injured tissues in a non-obese diabetes/severe combined immunodeficiency mouse model Br. J. Radiol., September 1, 2007; 80(Special_Issue_1): S49 - S55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Aurich, L. P Mueller, H. Aurich, J. Luetzkendorf, K. Tisljar, M. M Dollinger, W. Schormann, J. Walldorf, J. G Hengstler, W. E Fleig, et al. Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers Gut, March 1, 2007; 56(3): 405 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Makui, R. J. Soares, W. Jiang, M. Constante, and M. M. Santos Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading Blood, September 15, 2005; 106(6): 2189 - 2195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abedi, D. A. Greer, B. M. Foster, G. A. Colvin, J. A. Harpel, D. A. Demers, J. Pimentel, M. S. Dooner, and P. J. Quesenberry Critical variables in the conversion of marrow cells to skeletal muscle Blood, August 15, 2005; 106(4): 1488 - 1494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sato, H. Araki, J. Kato, K. Nakamura, Y. Kawano, M. Kobune, T. Sato, K. Miyanishi, T. Takayama, M. Takahashi, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion Blood, July 15, 2005; 106(2): 756 - 763. [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]
|
|
|
|
|
|
G. Almeida-Porada, C. D. Porada, J. Chamberlain, A. Torabi, and E. D. Zanjani Formation of human hepatocytes by human hematopoietic stem cells in sheep Blood, October 15, 2004; 104(8): 2582 - 2590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Doyonnas, M. A. LaBarge, A. Sacco, C. Charlton, and H. M. Blau Hematopoietic contribution to skeletal muscle regeneration by myelomonocytic precursors PNAS, September 14, 2004; 101(37): 13507 - 13512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Munoz-Elias, A. J. Marcus, T. M. Coyne, D. Woodbury, and I. B. Black Adult Bone Marrow Stromal Cells in the Embryonic Brain: Engraftment, Migration, Differentiation, and Long-Term Survival J. Neurosci., May 12, 2004; 24(19): 4585 - 4595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M R Alison, R Poulsom, W R Otto, P Vig, M Brittan, N C Direkze, M Lovell, T C Fang, S L Preston, and N A Wright Recipes for adult stem cell plasticity: fusion cuisine or readymade? J. Clin. Pathol., February 1, 2004; 57(2): 113 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Terai, I. Sakaida, N. Yamamoto, K. Omori, T. Watanabe, S. Ohata, T. Katada, K. Miyamoto, K. Shinoda, H. Nishina, et al. An In Vivo Model for Monitoring Trans-Differentiation of Bone Marrow Cells into Functional Hepatocytes J. Biochem., October 1, 2003; 134(4): 551 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, S. Ge, G. McNamara, Q.-L. Hao, G. M. Crooks, and J. A. Nolta Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells Blood, May 15, 2003; 101(10): 4201 - 4208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Tanimizu, M. Nishikawa, H. Saito, T. Tsujimura, and A. Miyajima Isolation of hepatoblasts based on the expression of Dlk/Pref-1 J. Cell Sci., May 1, 2003; 116(9): 1775 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Galli, A. Gritti, L. Bonfanti, and A. L. Vescovi Neural Stem Cells: An Overview Circ. Res., April 4, 2003; 92(6): 598 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S L Preston, M R Alison, S J Forbes, N C Direkze, R Poulsom, and N A Wright The new stem cell biology: something for everyone Mol. Pathol., April 1, 2003; 56(2): 86 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Alison, R. Poulsom, W. R. Otto, P. Vig, M. Brittan, N. C. Direkze, S. L. Preston, and N. A. Wright Plastic adult stem cells: will they graduate from the school of hard knocks? J. Cell Sci., February 15, 2003; 116(4): 599 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lechner and J. F. Habener Stem/progenitor cells derived from adult tissues: potential for the treatment of diabetes mellitus Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E259 - E266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Mitchell and N. Fausto Bone Marrow-Derived Hepatocytes : Rare but Promising Am. J. Pathol., August 1, 2002; 161(2): 349 - 350. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
