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Tracking long-term survival of intramyocardially delivered human adipose tissue-derived stem cells using bioluminescence imaging.
MedLine Citation:
PMID:  20730500     Owner:  NLM     Status:  In-Data-Review    
PURPOSE: Transplantation of a regenerative cell population derived from human subcutaneous adipose tissue (hASCs) for cardiac regeneration represents a promising therapy due to the capacity of these cells for proliferation and differentiation. Understanding the fate of injected hASCs would help to understand how hASCs work in vivo. The aim of this study was to track the long-term fate, including survival, differentiation, proliferation, apoptosis, migration, and growth factor secretion of intramyocardially injected hASCs following experimental acute myocardial infarction in an immunodeficient mouse model.
METHODS: Myocardial infarction was experimentally induced in severe combined immunodeficient mice by permanent ligation of the left anterior descending coronary artery. Lentivirally labeled hASCs (5 × 10(5); expressing green fluorescence protein [GFP] and luciferase) were injected into the peri-infarct region. Colony formation, growth kinetics, and differentiation of transduced hASCs were analyzed in vitro and compared to those of untransduced hASCs. The survival and migration of injected hASCs were tracked by luciferase-based bioluminescence imaging for 10 weeks. Immunofluorescence and terminal deoxynucleotidyl transferase dUTP nick end labeling staining were used to assess differentiation, proliferation, growth factor expression, or apoptosis of grafted hASCs in infarcted hearts and potential distribution to other tissues.
RESULTS: Lentivirus transduction and GFP and luciferase expression did not influence proliferation or differentiation of hASCs. Bioluminescence imaging demonstrated that injected hASCs survived in infarcted hearts during the follow-up of 10 weeks. Immunofluorescence confirmed that hASCs engrafted in ischemic hearts expressed bFGF and IGF-1, and did not migrate into other organs. Of all engrafted hASCs, 3.5% differentiated into cardiomyocytes or endothelial cells. Other cells maintained their proliferative potential or underwent apoptosis.
CONCLUSION: Luciferase-based bioluminescence imaging allows long-term tracking of intramyocardially injected hASCs in living mice. The hASCs might enhance function of injured hearts through long-term engraftment, growth factor secretion, and transdifferentiation to cardiomyocytes and endothelial cells.
Xiaowen Bai; Yasheng Yan; Michael Coleman; Grace Wu; Brian Rabinovich; Max Seidensticker; Eckhard Alt
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging     Volume:  13     ISSN:  1860-2002     ISO Abbreviation:  Mol Imaging Biol     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101125610     Medline TA:  Mol Imaging Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  633-45     Citation Subset:  IM    
Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, SCRB2, Unit 951, 7435 Fannin Street, Houston, TX, 77054, USA.
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