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 CD451 or CD45 1 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;56:1557-1566

Selenium levels in patients with hepatitis C virus-related chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma: A pilot study

“…We prefer the former hypothesis, because the population was maintained in liver grafts after extensive perfusion, but we did not exclude the probability of blood HSPCs in liver grafts. 1 With great interest we read the recent article in HEPATOLOGY by Rohr-Udilova et al, 1 who showed that reduced selenium (Se) levels and the subsequent reduced oxidative capacity lead to the accumulation of lipid peroxides producing reactive oxygen species (ROS) in patients with hepatocellular carcinoma (HCC). They set out to determine the effect of low Se levels on vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) expression, both of which are crucial in the development and growth of HCC.…”

“…1 Despite the valuable information added by the study, some issues caught our attention and, if clarified by the investigators, may greatly contribute to the knowledge on human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfection.…”

Natural Killer Cells and Liver Transplantation: Orchestrators of Rejection or Tolerance?

“…Phenotypically, hepatic NK cells have an activated phenotype with increased expression of the activation marker CD69 and the natural cytotoxicity receptor NKp44 ( There is accumulating evidence that the adult liver supports lymphopoiesis, and at least a proportion of hepatic NK cells may differentiate in situ from hematopoietic progenitors in the liver (12,13). NK cell precursors, isolated from adult liver, have been differentiated into functionally mature CD56 Bright and CD56 Dim NK cells, in vitro (14).…”

Donor-derived long-lived intragraft leukocytes are likely generated by hematopoietic stem/progenitor cells in liver

“…In this sense, the findings by Shi et al prove our hypothesis. 1 Regarding the origin of HSPCs, both consistent presences in liver or from blood HSPCs are possible. We prefer the former hypothesis, because the population was maintained in liver grafts after extensive perfusion, but we did not exclude the probability of blood HSPCs in liver grafts.…”

“…We prefer the former hypothesis, because the population was maintained in liver grafts after extensive perfusion, but we did not exclude the probability of blood HSPCs in liver grafts. 1 With great interest we read the recent article in HEPATOLOGY by Rohr-Udilova et al, 1 who showed that reduced selenium (Se) levels and the subsequent reduced oxidative capacity lead to the accumulation of lipid peroxides producing reactive oxygen species (ROS) in patients with hepatocellular carcinoma (HCC). They set out to determine the effect of low Se levels on vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) expression, both of which are crucial in the development and growth of HCC.…”