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  Towards a Diverse Research Environment

  Proteomic Study on
Nuclear Reprogramming During Cell Differentiation

  Molecular and Cellular Mechanisms of Hypoxia/HIFα Pathway in Regulating Biological Behaviour of
Mesenchymal Stem Cells

  The Link between Adult Stem Cells and Chimerism of Liver Transplantation

  Chungking Mansions as a 'Global Building'

  The Great Kanto Earthquake and the Political and Ideological Use of Catastrophe in Japan

  Historical Frontiers:
A Study of the May Fourth Spiritual Interpretation and
Development in the Context of Hong Kong


  RGC Collaborative Research Fund - Layman Summaries of Projects Funded in 2011/12 Exercise




Research group includes liver transplantation surgeons and research scientists

Topic: Liver transplantation (LT) is a cure for many liver diseases. Blood chimerism of donor origin can develop after LT, which could be a desirable situation after LT because the chimerism is often associated with transplanted liver tolerance. Blood chimerism formation in LT patients raises the possibility of existence of hematopoietic stem/progenitor cells (HSPCs) in liver. In this study, we characterized the blood cell chimerism of donor origin in a large cohort of LT patients, and analyzed putative HSPCs in adult human livers. 

Methodology: Human specimens included blood DNA from LT patients and a wedge of the liver tissue from donor liver graft. Polymorphic microsatellite marker (PCR), flow cytometry analysis, cell sorting, hematopoietic colony formation, and transplantation and engraftment in NOD-SCID mice.

 

 

 

 

Research Findings: Of over 200 LT patients investigated, the overall incidence of blood chimerism was around 6%. The incidence was significantly higher among patients tested shortly after LT (1 day to < 6 months) than in long-term LT patients (6 months to 8 years), although blood chimerism was indeed observed in long-term LT survival patients (4-5 years after LT). In human adult liver graft, we detected a small amount of hematopoietic Lin–CD34+CD38–CD90+ population representing putative HSPCs. Both Lin–CD34+ and Lin–CD45+ liver cells were capable of forming myeloid-lineage and erythroid-lineage methylcellulose colonies; more importantly, Lin–CD45+ or CD45+ liver cells could be engrafted into hematopoietic cells in immunodeficient mice. Thus, we provide the first evidence of a putative HSPC population in the adult human liver, with the liver acting as a good ectopic niche.

Implications: For the first time, our study demonstrates the presence of the putative HSPC population in adult human liver. Therefore, for LT patients, transient chimerism results from mature leucocytes and long-term chimerism derives from putative HSPCs in the liver graft. The discovery of existence of HSPCs in adult liver will have new implications for the understanding of extra-marrow hematopoiesis, liver regeneration, mechanisms of tolerance in organ transplantation and de novo cancer recurrence in LT patients.

Dr Xiao-Qi WANG
Department of Surgery
The University of Hong Kong

xqwang@hku.hk

 

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