title: Concomitant Retrograde Coronary Venous Infusion of Basic Fibroblast Growth Factor Enhances Engraftment and Differentiation of Bone Marrow Mesenchymal Stem Cells for Cardiac Repair after Myocardial Infarction.
abstract: OBJECTIVE
  Basic fibroblast growth factor (bFGF) increases the migration and viability of bone marrow mesenchymal stem cells (MSCs) in vitro. Retrograde coronary venous infusion can provide both increased regional bFGF concentrations and homogeneous cell dissemination. We determined whether retrograde delivery of bFGF enhances the potency of transplanted MSCs for cardiac repair in a canine infarct model.
  
  
  RESULTS
  Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype. A canine infarct model was employed by coronary ligation. One week later, animals were subjected to retrograde infusion of combination bFGF (200ng/mL) and MSCs (1×10(8) cells) (n=5), MSCs (1×10(8) cells, n=5), bFGF (200ng/mL, n=5), or placebo (phosphate-buffered saline, n=3). Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p<0.01 vs pre-infusion), and the treatment effect (delta LVEF) was greater in the bFGF+MSCs group compared to saline (7.43±1.51% versus -10.07±2.94%; p<0.001). Morphologic analysis revealed an increased infarct wall thickness in the bFGF+MSCs group compared to all others (p<0.05), accompanied by increased vascular density and reduced apoptosis. Immunofluorescence demonstrated increased cell engraftment and enhanced vascular differentiation in the bFGF+MSCs group compared to MSCs alone (p<0.05).
  
  
  CONCLUSIONS
  Retrograde coronary venous bFGF infusion augments engraftment and differentiation capacity of transplanted MSCs, recovering cardiac function and preventing adverse remodeling. This novel combined treatment and delivery method is a promising strategy for cardiac repair after ischemic injury.
authors.affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;
authors.forename: Lei
authors.initials: L
authors.lastname: Zhen
authors.affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;
authors.forename: Huangtai
authors.initials: H
authors.lastname: Miao
authors.affiliation: 2. Department of Ultrasound, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Sun
authors.affiliation: 2. Department of Ultrasound, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;
authors.forename: Bin
authors.initials: B
authors.lastname: Que
authors.affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;
authors.forename: Edmundo Patricio
authors.initials: EP
authors.lastname: Lopes Lao
authors.affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;
authors.forename: Xingxin
authors.initials: X
authors.lastname: Wu
authors.affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;
authors.forename: Shutian
authors.initials: S
authors.lastname: Shi
authors.affiliation: 3. Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Wayne B
authors.initials: WB
authors.lastname: Lau
authors.affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China; ; 3. Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ma
authors.affiliation: 4. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Ma
authors.affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;
authors.forename: Shaoping
authors.initials: S
authors.lastname: Nie
mesh_terms: D000818:Animals; D001699:Biometry; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006321:Heart / Q000033:anatomy & histology; D006651:Histocytochemistry; D007262:Infusions, Intravenous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008853:Microscopy; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D016222:Fibroblast Growth Factor 2
keywords: Cell transplantation; Growth factor; Mesenchymal stem cells; Myocardial infarction; Retrograde.