Imaging Survival and Function of Transplanted Cardiac Resident Stem Cells

Zongjin Li, Andrew Lee, Mei Huang, Hyung Chun, Jaehoon Chung, Pauline Chu, Grant Hoyt, Phillip Yang, Jarrett Rosenberg, Robert C. Robbins, Joseph C. Wu

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Objectives: 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 × 105 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.

Original languageEnglish (US)
Pages (from-to)1229-1240
Number of pages12
JournalJournal of the American College of Cardiology
Volume53
Issue number14
DOIs
StatePublished - Apr 7 2009
Externally publishedYes

Keywords

  • cardiac stem cells
  • cell fate
  • differentiation
  • ischemic heart disease
  • molecular imaging

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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