Early stem cell engraftment predicts late cardiac functional recovery preclinical insights from molecular imaging

Junwei Liu, Kazim H. Narsinh, Feng Lan, Li Wang, Patricia K. Nguyen, Shijun Hu, Andrew Lee, Leng Han, Yongquan Gong, Mei Huang, Divya Nag, Jarrett Rosenberg, Alexandra Chouldechova, Robert C. Robbins, Joseph C. Wu

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)481-490
Number of pages10
JournalCirculation: Cardiovascular Imaging
Volume5
Issue number4
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • Cardiac progenitor cells
  • Cell therapy
  • Positron emission tomography
  • Stem cells

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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