Document Detail


Early stem cell engraftment predicts late cardiac functional recovery: preclinical insights from molecular imaging.
MedLine Citation:
PMID:  22565608     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-07
Journal Detail:
Title:  Circulation. Cardiovascular imaging     Volume:  5     ISSN:  1942-0080     ISO Abbreviation:  Circ Cardiovasc Imaging     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-19     Completed Date:  2012-10-24     Revised Date:  2013-07-04    
Medline Journal Info:
Nlm Unique ID:  101479935     Medline TA:  Circ Cardiovasc Imaging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  481-90     Citation Subset:  IM    
Affiliation:
Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Cell Survival
Disease Models, Animal
Echocardiography
Gene Transfer Techniques
Genes, Reporter / genetics
Genetic Therapy
Guanine / analogs & derivatives
Humans
Immunohistochemistry
Laser Capture Microdissection
Linear Models
Magnetic Resonance Imaging
Mice
Mice, SCID
Myocardial Contraction / physiology
Myocardial Infarction / physiopathology,  radionuclide imaging*,  therapy*
Myocytes, Cardiac / transplantation*
Paracrine Communication / physiology
Phenotype
Positron-Emission Tomography / methods*
Recovery of Function
Stem Cell Transplantation*
Thymidine Kinase / genetics,  metabolism
Viral Proteins / metabolism
Grant Support
ID/Acronym/Agency:
R01 EB009689/EB/NIBIB NIH HHS; R01 HL093172/HL/NHLBI NIH HHS; R01EB009689/EB/NIBIB NIH HHS; R01HL093172/HL/NHLBI NIH HHS; RC1 HL099117/HL/NHLBI NIH HHS; RC1HL099117/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/9-(4-fluoro-3-hydroxymethylbutyl)guanine; 0/Viral Proteins; 73-40-5/Guanine; EC 2.7.1.21/Thymidine Kinase
Comments/Corrections

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