title: Endothelial fate and angiogenic properties of human CD34+ progenitor cells in zebrafish.
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.
  
  
  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.
  
  
  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.
authors.affiliation: Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Via Parea 4, 20138 Milan, Italy. ombretta.pozzoli@ccfm.it
authors.forename: Ombretta
authors.initials: O
authors.lastname: Pozzoli
authors.forename: Pietro
authors.initials: P
authors.lastname: Vella
authors.forename: Grazia
authors.initials: G
authors.lastname: Iaffaldano
authors.forename: Valeria
authors.initials: V
authors.lastname: Parente
authors.forename: Paolo
authors.initials: P
authors.lastname: Devanna
authors.forename: Marta
authors.initials: M
authors.lastname: Lacovich
authors.forename: Carla Lora
authors.initials: CL
authors.lastname: Lamia
authors.forename: Umberto
authors.initials: U
authors.lastname: Fascio
authors.forename: Daniela
authors.initials: D
authors.lastname: Longoni
authors.forename: Franco
authors.initials: F
authors.lastname: Cotelli
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pesce
mesh_terms: D000671:Amputation, Surgical; D058500:Animal Fins / Q000098:blood supply* / Q000601:surgery; D000818:Animals; D030801:Animals, Genetically Modified; D018952:Antigens, CD34 / Q000032:analysis*; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D036101:Cord Blood Stem Cell Transplantation; D042783:Endothelial Cells / Q000276:immunology / Q000637:transplantation*; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D018507:Gene Expression Regulation, Developmental; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D010641:Phenotype; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D011993:Recombinant Fusion Proteins; D042582:Vascular Endothelial Growth Factor C; D029961:Zebrafish Proteins; C493178:vascular endothelial growth factor C, zebrafish