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Hematopoietic chimerism in liver transplantation patients and hematopoietic stem/progenitor cells in adult human liver†
Article first published online: 4 OCT 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 4, pages 1557–1566, October 2012
How to Cite
Wang, X. Q., Lo, C. M., Chen, L., Cheung, C. K.Y., Yang, Z. F., Chen, Y. X., Ng, M. N., Yu, W. C., Ming, X., Zhang, W., Ho, D. W.Y., Chan, S. C. and Fan, S. T. (2012), Hematopoietic chimerism in liver transplantation patients and hematopoietic stem/progenitor cells in adult human liver. Hepatology, 56: 1557–1566. doi: 10.1002/hep.25820
Potential conflict of interest: Nothing to report.
- Issue published online: 4 OCT 2012
- Article first published online: 4 OCT 2012
- Accepted manuscript online: 27 APR 2012 10:32AM EST
- Manuscript Accepted: 23 APR 2012
- Manuscript Received: 23 NOV 2011
- General Research Fund of the Hong Kong Research Grant Council. Grant Number: HKU 778809M; to X.Q.W.
- Seed Funding Program for Basic Research of Hong Kong University. Grant Number: 59162; to X.Q.W.
Liver transplantation (LT) is a cure for many liver diseases. Blood chimerism of donor origin can develop after LT, which raises the possibility of the existence of hematopoietic stem/progenitor cells (HSPCs) in the liver. We characterized the blood chimerism in a large cohort of 249 LT patients and analyzed putative HSPCs in adult human livers. The overall incidence of chimerism was 6.43%, of which 11.11% was among short-term (1 day to 6 months) and 3.77% was among long-term (6 months to 8 years) LT patients. Hematopoietic Lin−CD34+CD38−CD90+ populations have been demonstrated to generate long-term lymphomyeloid grafts in transplantations. In human adult livers, we detected Lin−CD34+CD38−CD90+ populations accounting for 0.03% ± 0.017% of the total single liver cells and for 0.05% ± 0.012% of CD45+ liver cells. Both Lin−CD34+ and Lin−CD45+ liver cells, from extensively perfused human liver grafts, were capable of forming hematopoietic myeloid-lineage and erythroid-lineage methylcellulose colonies. More importantly, Lin−CD45+ or CD45+ liver cells could be engrafted into hematopoietic cells in an immunodeficient mouse model. These results are the first evidence of the presence of putative HSPC populations in the adult human liver, where the liver is a good ectopic niche. The discovery of the existence of HSPCs in the adult liver have implications for the understanding of extramarrow hematopoiesis, liver regeneration, mechanisms of tolerance in organ transplantation, and de novo cancer recurrence in LT patients. Conclusion: The human adult liver contains a small population of HSPCs. In LT patients, there are two types of chimerisms: transient chimerism, resulting from mature leucocytes, and long-term chimerism, derived from putative HSPCs in the liver graft. (HEPATOLOGY 2012)