title: Targeted delivery of vascular endothelial growth factor improves stem cell therapy in a rat myocardial infarction model.
abstract: Rebuilding of infarcted myocardium by mesenchymal stem cells (MSCs) has not been successful because of poor cell survival due in part to insufficient blood supply after myocardial infarction (MI). We hypothesize that targeted delivery of vascular endothelial growth factor (VEGF) to MI can help regenerate vasculature in support of MSC therapy in a rat model of MI. VEGF-encapsulated immunoliposomes targeting overexpressed P-selectin in MI tissue were infused by tail vein immediately after MI. One week later, MSCs were injected intramyocardially. The cardiac function loss was moderated slightly by targeted delivery of VEGF or MSC treatment. Targeted VEGF+MSC combination treatment showed highest attenuation in cardiac function loss. The combination treatment also increased blood vessel density (80%) and decreased collagen content in post-MI tissue (33%). Engraftment of MSCs in the combination treatment group was significantly increased and the engrafted cells contributed to the restoration of blood vessels.
  
  
  BACKGROUND
  VEGF immunoliposomes targeting myocardial infarction tissue resulted in significantly higher attenuation of cardiac function loss when used in combination with mesenchymal stem cells. MSCs were previously found to have poor ability to restore cardiac tissue, likely as a result of poor blood supply in the affected areas. This new method counterbalances that weakness by the known effects of VEGF, as demonstrated in a rat model.
authors.affiliation: Department of Biomedical Engineering, Widener University, Chester, PA USA; Department of Mechanical Engineering, Temple University, Philadelphia, PA USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Gan
authors.affiliation: Department of Mechanical Engineering, Temple University, Philadelphia, PA USA.
authors.forename: Rabe'e
authors.initials: R
authors.lastname: Cheheltani
authors.affiliation: Department of Mechanical Engineering, Temple University, Philadelphia, PA USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Curran
authors.affiliation: Department of Mechanical Engineering, Temple University, Philadelphia, PA USA.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Lamberti
authors.affiliation: Shriners Hospitals Pediatric Research Center and Department of Neurology, Temple University School of Medicine, Philadelphia, PA USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Krynska
authors.affiliation: Department of Mechanical Engineering, Temple University, Philadelphia, PA USA.
authors.forename: Mohammad F
authors.initials: MF
authors.lastname: Kiani
authors.affiliation: Department of Biomedical Engineering, Widener University, Chester, PA USA; Department of Mechanical Engineering, Temple University, Philadelphia, PA USA. Electronic address: bwang@wumail.widener.edu.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000628:therapy*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D003094:Collagen
keywords: Angiogenesis; Liposome; Mesenchymal stem cells; Myocardial infarction; Myocardial infarction animal model