title: Early stem cell engraftment predicts late cardiac functional recovery: preclinical insights from molecular imaging.
abstract: BACKGROUND
  Human cardiac progenitor cells have demonstrated great potential for myocardial repair in small and large animals, but robust methods for longitudinal assessment of their engraftment in humans is not yet readily available. In this study, we sought to optimize and evaluate the use of positron emission tomography (PET) reporter gene imaging for monitoring human cardiac progenitor cell (hCPC) transplantation in a mouse model of myocardial infarction.
  
  
  RESULTS
  hCPCs were isolated and expanded from human myocardial samples and stably transduced with herpes simplex virus thymidine kinase (TK) PET reporter gene. Thymidine kinase-expressing hCPCs were characterized in vitro and transplanted into murine myocardial infarction models (n=57). Cardiac echocardiographic, magnetic resonance imaging and pressure-volume loop analyses revealed improvement in left ventricular contractile function 2 weeks after transplant (hCPC versus phosphate-buffered saline, P<0.03). Noninvasive PET imaging was used to track hCPC fate over a 4-week time period, demonstrating a substantial decline in surviving cells. Importantly, early cell engraftment as assessed by PET was found to predict subsequent functional improvement, implying a "dose-effect" relationship. We isolated the transplanted cells from recipient myocardium by laser capture microdissection for in vivo transcriptome analysis. Our results provide direct evidence that hCPCs augment cardiac function after their transplantation into ischemic myocardium through paracrine secretion of growth factors.
  
  
  CONCLUSIONS
  PET reporter gene imaging can provide important diagnostic and prognostic information regarding the ultimate success of hCPC treatment for myocardial infarction.
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Junwei
authors.initials: J
authors.lastname: Liu
authors.forename: Kazim H
authors.initials: KH
authors.lastname: Narsinh
authors.forename: Feng
authors.initials: F
authors.lastname: Lan
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Nguyen
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.forename: Andrew
authors.initials: A
authors.lastname: Lee
authors.forename: Leng
authors.initials: L
authors.lastname: Han
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Gong
authors.forename: Mei
authors.initials: M
authors.lastname: Huang
authors.forename: Divya
authors.initials: D
authors.lastname: Nag
authors.forename: Jarrett
authors.initials: J
authors.lastname: Rosenberg
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chouldechova
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival; D004195:Disease Models, Animal; D004452:Echocardiography; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D015316:Genetic Therapy; D006147:Guanine / Q000031:analogs & derivatives; D006801:Humans; D007150:Immunohistochemistry; D061346:Laser Capture Microdissection; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D051379:Mice; D016513:Mice, SCID; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000637:transplantation*; D019899:Paracrine Communication / Q000502:physiology; D010641:Phenotype; D049268:Positron-Emission Tomography / Q000379:methods*; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
chemical_list: C113308:9-(4-fluoro-3-hydroxymethylbutyl)guanine; D014764:Viral Proteins; D006147:Guanine; D013937:Thymidine Kinase