Liver sinusoidal endothelial and biliary cell repopulation following irradiation and partial hepatectomy

AIM: To investigate whether irradiation (IR) and partial hepatectomy (PH) may prepare the host liver for nonparenchymal cell (NPC) transplantation.METHODS: Livers of dipeptidyl peptidase(DPP)-deficient rats were pre-conditioned with external beam IR (25 Gy) delivered to two-thirds of the right liver lobules followed by a one-third PH of the untreated lob-ule. DPP-positive liver cells (NPC preparations enriched for liver sinusoidal endothelial cells (LSECs) and hepatocytes) were transplanted via the spleen into the recipient livers. The extent and quality of donor cell engraftment and growth was studied over a long-term interval of 16 wk after transplantation.RESULTS: Host liver staining demonstrated 3 different repopulation types. Well def ined clusters of donor-derived hepatocytes with canalicular expression of DPP were detectable either adjacent to or in between large areas of donor cells (covering up to 90% of the section plane) co-expressing the endothelial marker platelet endothelial cell adhesion molecule. The third type consisted of formations of DPP-positive duct-like structures which co-localized with biliary epithelial CD49f.CONCLUSION: Liver IR and PH as a preconditioning stimulus enables multiple cell liver repopulation by donor hepatocytes, LSECs, and bile duct cells.

Cell competition in liver carcinogenesis

Cell competition is now a well-established quality control strategy to optimize cell and tissue fitness in multicellular organisms.While pursuing this goal,it is also effective in selecting against altered/defective cells with putative(pre)-neoplastic potential,thereby edging the risk of cancer development.The flip side of the coin is that the molecular machinery driving cell competition can also be co-opted by neoplastic cell populations to expand unchecked,outside the boundaries of tissue homeostatic control.This review will focus on information that begins to emerge regarding the role of cell competition in liver physiology and pathology.Liver repopulation by normal transplanted hepatocytes is an interesting field of investigation in this regard.The biological coordinates of this process share many features suggesting that cell competition is a driving force for the clearance of endogenous damaged hepatocytes by normal donor-derived cells,as previously proposed.Intriguing analogies between liver repopulation and carcinogenesis will be briefly discussed and the potential dual role of cell competition,as a barrier or a spur to neoplastic development,will be considered.Cell competition is in essence a cooperative strategy organized at tissue level.One facet of such cooperative attitude is expressed in the elimination of altered cells which may represent a threat to the organismal community.On the other hand,the society of cells can be disrupted by the emergence of selfish clones,exploiting the molecular bar codes of cell competition,thereby paving their way to uncontrolled growth.