title: Hematopoietic chimerism in liver transplantation patients and hematopoietic stem/progenitor cells in adult human liver.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong, China.
authors.forename: Xiao Qi
authors.initials: XQ
authors.lastname: Wang
authors.forename: Chung Mau
authors.initials: CM
authors.lastname: Lo
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Cindy K Y
authors.initials: CK
authors.lastname: Cheung
authors.forename: Zhen Fan
authors.initials: ZF
authors.lastname: Yang
authors.forename: Yong Xiong
authors.initials: YX
authors.lastname: Chen
authors.forename: Michael N
authors.initials: MN
authors.lastname: Ng
authors.forename: Wan Ching
authors.initials: WC
authors.lastname: Yu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ming
authors.forename: Wu
authors.initials: W
authors.lastname: Zhang
authors.forename: David W Y
authors.initials: DW
authors.lastname: Ho
authors.forename: See Ching
authors.initials: SC
authors.lastname: Chan
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D046528:Chimerism; D015331:Cohort Studies; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006410:Hematopoiesis / Q000276:immunology / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D016031:Liver Transplantation / Q000276:immunology* / Q000379:methods; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014019:Tissue Donors; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D015703:Antigens, CD