Vasculogenic potential of long term repopulating cord blood progenitors.
In the adult, involvement of bone marrow-derived circulating endothelial progenitor cells (EPCs) in tissue revascularization (vasculogenesis) and the cooperation of hematopoietic cell subsets in supporting this process have been described in different experimental animal models. However, the effective contribution of such cells in restoring organ vascularization in a clinical setting needs to be clarified. In this study, a mouse transplantation model was engrafted by human cord blood hematopoietic stem and progenitor cells to follow the behavior of donor-derived endothelial and hematopoietic cells in the presence of a localized source of an angiogenic inducer. Human endothelial markers (CD31+/CD45-, VE-cadherin+) were always detectable in the bone marrow of transplanted mice, while they were only randomly detectable in peripheral neovascularization sites. To investigate the ability of human transplanted hematopoietic stem cells to support new vessel formation in response to altered homeostatic conditions, chimeric mice were further treated by systemic injection of human mononuclear cells (MNCs). Our data indicate that MNC administration in transplanted mice enhances vasculogenesis in the newly formed vessels. Taken together these results suggest that human-derived EPCs, long-term engrafting a xenotransplantation model, have hematopoietic and endothelial developmental potential, which can be modulated by altering the physiological conditions of host microenvironment.
Droetto
Sara
S
Division of Molecular Angiogenesis, I.R.C.C., Strada Provinciale 142, Km 3.95, Candiolo (TO), Italy. sara.droetto@ircc.it
Viale
Andrea
A
Primo
Luca
L
Jordaney
Noela
N
Bruno
Stefania
S
Pagano
Marco
M
Piacibello
Wanda
W
Bussolino
Federico
F
Aglietta
Massimo
M
D000818:Animals; D015415:Biomarkers; D001773:Blood Cells / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D002196:Capillaries / Q000166:cytology; D019070:Cell Lineage; D003094:Collagen; D036101:Cord Blood Stem Cell Transplantation; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology*; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D017930:Genes, Reporter; D006085:Graft Survival; D006801:Humans; D007797:Laminin; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018919:Neovascularization, Physiologic; D011509:Proteoglycans; D011828:Radiation Chimera; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D015415:Biomarkers; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen