title: Imaging survival and function of transplanted cardiac resident stem cells.
abstract: OBJECTIVE
  The goal of this study is to characterize resident cardiac stem cells (CSCs) and investigate their therapeutic efficacy in myocardial infarction by molecular imaging methods.
  
  
  BACKGROUND
  CSCs have been isolated and characterized in vitro. These cells offer a provocative method to regenerate the damaged myocardium. However, the survival kinetics and function of transplanted CSCs have not been fully elucidated.
  
  
  METHODS
  CSCs were isolated from L2G85 transgenic mice (FVB strain background) that constitutively express both firefly luciferase and enhanced green fluorescence protein reporter gene. CSCs were characterized in vitro and transplanted in vivo into murine infarction models. Multimodality noninvasive imaging techniques were used to assess CSC survival and therapeutic efficacy for restoration of cardiac function.
  
  
  RESULTS
  CSCs can be isolated from L2G85 mice, and fluorescence-activated cell sorting analysis showed expression of resident CSC markers (Sca-1, c-Kit) and mesenchymal stem cell markers (CD90, CD106). Afterwards, 5 x 10(5) CSCs (n = 30) or phosphate-buffered saline control (n = 15) was injected into the hearts of syngeneic FVB mice undergoing left anterior descending artery ligation. Bioluminescence imaging showed poor donor cell survival by week 8. Echocardiogram, invasive hemodynamic pressure-volume analysis, positron emission tomography imaging with fluorine-18-fluorodeoxyglucose, and cardiac magnetic resonance imaging demonstrated no significant difference in cardiac contractility and viability between the CSC and control group. Finally, postmortem analysis confirmed transplanted CSCs integrated with host cardiomyocytes by immunohistology.
  
  
  CONCLUSIONS
  In a mouse myocardial infarction model, Sca-1-positive CSCs provide no long-term engraftment and benefit to cardiac function as determined by multimodality imaging.
authors.affiliation: Department of Radiology and Molecular Imaging Program (MIPS), Stanford University School of Medicine, Stanford, California 94305-5344, USA.
authors.forename: Zongjin
authors.initials: Z
authors.lastname: Li
authors.forename: Andrew
authors.initials: A
authors.lastname: Lee
authors.forename: Mei
authors.initials: M
authors.lastname: Huang
authors.forename: Hyung
authors.initials: H
authors.lastname: Chun
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Chung
authors.forename: Pauline
authors.initials: P
authors.lastname: Chu
authors.forename: Grant
authors.initials: G
authors.lastname: Hoyt
authors.forename: Phillip
authors.initials: P
authors.lastname: Yang
authors.forename: Jarrett
authors.initials: J
authors.lastname: Rosenberg
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu