Human fetal aorta contains vascular progenitor cells capable of inducing vasculogenesis, angiogenesis, and myogenesis in vitro and in a murine model of peripheral ischemia.
Vasculogenesis, the formation of blood vessels in embryonic or fetal tissue mediated by immature vascular cells (ie, angioblasts), is poorly understood. We report the identification of a population of vascular progenitor cells (hVPCs) in the human fetal aorta composed of undifferentiated mesenchymal cells that coexpress endothelial and myogenic markers. Under culture conditions that promoted cell differentiation, hVPCs gave rise to a mixed population of mature endothelial and mural cells when progenitor cells were stimulated with vascular endothelial growth factor-A or platelet-derived growth factor-betabeta. hVPCs grew as nonadherent cells and, when embedded in a three-dimensional collagen gel, reorganized into cohesive cellular cords that resembled mature vascular structures. hVPC-conditioned medium contained angiogenic substances (vascular endothelial growth factor-A and angiopoietin-2) and strongly stimulated the proliferation of endothelial cells. We also demonstrate the therapeutic efficacy of a small number of hVPCs transplanted into ischemic limb muscle of immunodeficient mice. hVPCs markedly improved neovascularization and inhibited the loss of endogenous endothelial cells and myocytes, thus ameliorating the clinical outcome from ischemia. We conclude that fetal aorta represents an important source for the investigation of the phenotypic and functional features of human vascular progenitor cells.
Invernici
Gloria
G
Neurobiology and Neuroregenerative Therapies Unit, Carlo Besta Neurological Institute, Milan 20133, Italy.
Emanueli
Costanza
C
Madeddu
Paolo
P
Cristini
Silvia
S
Gadau
Sergio
S
Benetti
Anna
A
Ciusani
Emilio
E
Stassi
Giorgio
G
Siragusa
Mauro
M
Nicosia
Roberto
R
Peschle
Cesare
C
Fascio
Umberto
U
Colombo
Augusto
A
Rizzuti
Tommaso
T
Parati
Eugenio
E
Alessandri
Giulio
G
D000071916:AC133 Antigen; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D001011:Aorta / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D000077214:Becaplermin; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology; D019070:Cell Lineage; D002478:Cells, Cultured; D005333:Fetus / Q000033:anatomy & histology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007511:Ischemia; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D013234:Stem Cells / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000071916:AC133 Antigen; D042702:Angiopoietin-2; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D006023:Glycoproteins; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin; D040301:Vascular Endothelial Growth Factor Receptor-2