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Content archived on 2024-05-29

ENDOTHELIN-3/ENDOTHELIN RECEPTOR B SIGNALING IN THE REGULATION OF NEURAL CREST STEM CELLS MIGRATION: THERAPEUTIC POTENTIAL FOR HIRSCHSPRUNG S DISEASE

Objective

Complete colonization of the gut by enteric neural precursors depends on activation of endothelin receptor B (EDNRB) by its ligand endothelin 3 (EDN3). Loss of EDN3/EDNRB signaling leads to aganglionosis of distal gut (Hirschsprung s disease, HSCR) caused by failure of neural crest stem cells (NCSCs) to migrate into the distal gut. We hypothesize that EDN3/EDNB-signalling is only involved in the migration of NCSC after embryonic day 12.5 during ENS development and is not necessary for proliferation, survival or differentiation of NCSCs in later stages. Thus, the migration defect caused by Ednrb deficiency could be bypassed by transplanting NCSCs directly into the aganglionic region of Ednrbsl/sl rats (spotting lethal rats that suffer of distal aganglionosis). We will analyze if transplanted NCSCs engraft and survive in the gut, undergo differentiation into functional enteric neurons and improve gut motor function. This study will provide evidence for stem cell replacement as a possible therapeutic tool.

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Keywords

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Topic(s)

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Call for proposal

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FP6-2004-MOBILITY-6
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Funding Scheme

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OIF - Marie Curie actions-Outgoing International Fellowships

Coordinator

UNIVERSITAT DE VALÈNCIA. ESTUDI GENERAL
EU contribution
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Total cost

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Participants (1)

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