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Endothelial fate and angiogenic properties of human CD34+ progenitor cells in zebrafish.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2011 Jul; Vol. 31 (7), pp. 1589-97. Date of Electronic Publication: 2011 Apr 28. - Publication Year :
- 2011
-
Abstract
- Objective: The vascular competence of human-derived hematopoietic progenitors for postnatal vascularization is still poorly characterized. It is unclear whether, in the absence of ischemia, hematopoietic progenitors participate in neovascularization and whether they play a role in new blood vessel formation by incorporating into developing vessels or by a paracrine action.<br />Methods and Results: In the present study, human cord blood-derived CD34(+) (hCD34(+)) cells were transplanted into pre- and postgastrulation zebrafish embryos and in an adult vascular regeneration model induced by caudal fin amputation. When injected before gastrulation, hCD34(+) cells cosegregated with the presumptive zebrafish hemangioblasts, characterized by Scl and Gata2 expression, in the anterior and posterior lateral mesoderm and were involved in early development of the embryonic vasculature. These morphogenetic events occurred without apparent lineage reprogramming, as shown by CD45 expression. When transplanted postgastrulation, hCD34(+) cells were recruited into developing vessels, where they exhibited a potent paracrine proangiogenic action. Finally, hCD34(+) cells rescued vascular defects induced by Vegf-c in vivo targeting and enhanced vascular repair in the zebrafish fin amputation model.<br />Conclusions: These results indicate an unexpected developmental ability of human-derived hematopoietic progenitors and support the hypothesis of an evolutionary conservation of molecular pathways involved in endothelial progenitor differentiation in vivo.
- Subjects :
- Amputation, Surgical
Animal Fins surgery
Animals
Animals, Genetically Modified
Caco-2 Cells
Cell Movement
Endothelial Cells immunology
Fetal Blood immunology
Gene Expression Regulation, Developmental
Humans
Paracrine Communication
Phenotype
RNA Interference
Recombinant Fusion Proteins metabolism
Regeneration
Signal Transduction
Vascular Endothelial Growth Factor C genetics
Vascular Endothelial Growth Factor C metabolism
Zebrafish Proteins genetics
Zebrafish Proteins metabolism
Animal Fins blood supply
Antigens, CD34 analysis
Cell Differentiation drug effects
Cord Blood Stem Cell Transplantation
Endothelial Cells transplantation
Fetal Blood cytology
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells immunology
Neovascularization, Physiologic
Zebrafish embryology
Zebrafish genetics
Zebrafish growth & development
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 31
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 21527751
- Full Text :
- https://doi.org/10.1161/ATVBAHA.111.226969