title: Heart infarct in NOD-SCID mice: therapeutic vasculogenesis by transplantation of human CD34+ cells and low dose CD34+KDR+ cells.
abstract: Hematopoietic (Hem) and endothelial (End) lineages derive from a common progenitor cell, the hemangioblast: specifically, the human cord blood (CB) CD34+KDR+ cell fraction comprises primitive Hem and End cells, as well as hemangioblasts. In humans, the potential therapeutic role of Hem and End progenitors in ischemic heart disease is subject to intense investigation. Particularly, the contribution of these cells to angiogenesis and cardiomyogenesis in myocardial ischemia is not well established. In our studies, we induced myocardial infarct (MI) in the immunocompromised NOD-SCID mouse model, and monitored the effects of myocardial transplantation of human CB CD34+ cells on cardiac function. Specifically, we compared the therapeutic effect of unseparated CD34+ cells vs. PBS and mononuclear cells (MNCs); moreover, we compared the action of the CD34+KDR+ cell subfraction vs. the CD34+KDR- subset. CD34+ cells significantly improve cardiac function after MI, as compared with PBS/MNCs. Similar beneficial actions were obtained using a 2-log lower number of CD34+KDR+ cells, while the same number of CD34+KDR- cells did not have any effects. The beneficial effect of CD34+KDR+ cells may mostly be ascribed to their notable resistance to apoptosis and to their angiogenic action, since cardiomyogenesis was limited. Altogether, our results indicate that, within the CD34+ cell population, the CD34+KDR+ fraction is responsible for the improvement in cardiac hemodynamics and hence represents the candidate active CD34+ cell subset.
authors.affiliation: Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, USA.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Botta
authors.forename: Erhe
authors.initials: E
authors.lastname: Gao
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stassi
authors.forename: Desirée
authors.initials: D
authors.lastname: Bonci
authors.forename: Elvira
authors.initials: E
authors.lastname: Pelosi
authors.forename: Donna
authors.initials: D
authors.lastname: Zwas
authors.forename: Mariella
authors.initials: M
authors.lastname: Patti
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Colonna
authors.forename: Marta
authors.initials: M
authors.lastname: Baiocchi
authors.forename: Simona
authors.initials: S
authors.lastname: Coppola
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Condorelli
authors.forename: Cesare
authors.initials: C
authors.lastname: Peschle
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis; D019898:Autocrine Communication / Q000187:drug effects; D002459:Cell Fusion; D019070:Cell Lineage; D017690:Cell Transplantation; D018920:Coculture Techniques; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D016276:Ventricular Function
chemical_list: D018952:Antigens, CD34; D016895:Culture Media, Serum-Free; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2