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RESEARCH PRODUCT
Heart infarct in NOD-SCID mice: therapeutic vasculogenesis by transplantation of human CD34+ cells and low dose CD34+KDR+ cells
Gianluigi CondorelliMarta BaiocchiDonna R. ZwasSimona CoppolaRosanna BottaMariella PattiDésirée BonciGiorgio StassiElvira PelosiErhe GaoXin MaCesare PeschleLucrezia Colonnasubject
Vascular Endothelial Growth Factor AneoangiogenesisTime FactorsAngiogenesisCell TransplantationHeart VentriclesCD34Myocardial InfarctionAntigens CD34ApoptosisMice SCIDBiologySCIDPeripheral blood mononuclear cellBiochemistryCulture Media Serum-FreeSerum-FreeCell FusionMiceVasculogenesisMice Inbred NODparasitic diseasesGeneticsAnimalsHumansVentricular Functionendothelial precursorsCell LineageProgenitor cellAntigensMolecular Biologyneoangiogenesis endothelial precursors hematopoietic stem cellsHemodynamicsFetal BloodVascular Endothelial Growth Factor Receptor-2Coculture Techniqueshematopoietic stem cellsCulture MediaTransplantationAutocrine CommunicationCord bloodImmunologycardiovascular systemCancer researchHemangioblastInbred NODCD34neoangiogenesis; endothelial precursors; hematopoietic stem cells; Animals; Antigens CD34; Apoptosis; Autocrine Communication; Cell Fusion; Cell Lineage; Coculture Techniques; Culture Media Serum-Free; Fetal Blood; Heart Ventricles; Hemodynamics; Humans; Mice; Mice Inbred NOD; Mice SCID; Myocardial Infarction; Time Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Ventricular Function; Cell Transplantation; Biotechnology; Biochemistry; Molecular Biology; GeneticsBiotechnologydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2004-01-01 |