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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
CD39 modulates hematopoietic stem cell recruitment and promotes liver regeneration in mice and humans after partial hepatectomy
Annals of Surgery, Volume 257, No. 4, Year 2013
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Description
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 Cd39 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. Copyright © 2013 by Lippincott Williams & Wilkins.
Authors & Co-Authors
Junger, Wolfgang Georg
United States, Boston
Beth Israel Deaconess Medical Center
Csizmadia, Eva
United States, Boston
Harvard Medical School
Karp, Seth J.
United States, Boston
Beth Israel Deaconess Medical Center
Knoefel, Wolfram Trudo
Germany, Dusseldorf
Universitätsklinikum Düsseldorf
Robson, Simon Christopher
United States, Boston
Harvard Medical School
Statistics
Citations: 28
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1097/SLA.0b013e31826c3ec2
ISSN:
15281140
Research Areas
Violence And Injury