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• W2080763896 abstract "In Brief Objective: To study molecular mechanisms involved in hematopoietic stem cell (HSC) mobilization after liver resection and determine impacts on liver regeneration. Background: Extracellular nucleotide-mediated cell signaling has been shown to boost liver regeneration. Ectonucleotidases of the CD39 family are expressed by bone marrow–derived cells, and purinergic mechanisms might also impact mobilization and functions of HSC after liver injury. Methods: Partial hepatectomy was performed in C57BL/6 wild-type, Cd39 ectonucleotidase-null mice and in chimeric mice after transplantation of wild-type or Cd39-null bone marrow. Bone marrow–derived HSCs were purified by fluorescence-activated cell sorting and administered after hepatectomy. Chemotactic studies were performed to examine effects of purinergic receptor agonists and antagonists in vitro. Mobilization of human HSCs and expression of CD39 were examined and linked to the extent of resection and liver tests. Results: Subsets of HSCs expressing Cd39 are preferentially mobilized after partial hepatectomy. Chemotactic responses of HSCs are increased by CD39-dependent adenosine triphosphate hydrolysis and adenosine signaling via A2A receptors in vitro. Mobilized Cd39high HSCs boost liver regeneration, potentially limiting interleukin 1β signaling. In clinical studies, mobilized human HSCs also express CD39 at high levels. Mobilization of HSCs correlates directly with the restoration of liver volume and function after partial hepatectomy. Conclusions: We demonstrate CD39 to be a novel HSC marker that defines a functionally distinct stem cell subset in mice and humans. HSCs are mobilized after liver resection, limit inflammation, and boost regeneration in a CD39-dependent manner. These observations have implications for monitoring and indicate future therapeutic avenues. CD39 is an ectonucleotidase that is expressed at high levels by functionally distinct subsets of hematopoietic stem cells (HSCs), which are preferentially mobilized after partial hepatectomy. These CD39-expressing HSCs augment liver regeneration in experimental mouse models and have potential relevance for monitoring and therapeutic interventions after liver resection." @default.
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• W2080763896 date "2013-04-01" @default.
• W2080763896 modified "2023-10-08" @default.
• W2080763896 title "CD39 Modulates Hematopoietic Stem Cell Recruitment and Promotes Liver Regeneration in Mice and Humans After Partial Hepatectomy" @default.
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• W2080763896 doi "https://doi.org/10.1097/sla.0b013e31826c3ec2" @default.
• W2080763896 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4243517" @default.
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