| Stimulation of adult resident cardiac progenitor cells by durable myocardial expression of thymosin beta 4 with ultrasound-targeted microbubble delivery. | |
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MedLine Citation:
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PMID: 23151517 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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It has been proposed that thymosin beta 4 (TB4)-protein delivery stimulates differentiation of resident adult WT1-positive cardiac progenitor cells, but with very low efficiency. We determined whether gene therapy with human TB4 stimulates proliferation of resident adult cardiac progenitor cells in normal rat heart. Ultrasound-targeted microbubble destruction (UTMD) was used to deliver the human TB4 gene under a piggybac transposon plasmid to normal rat heart. The rat hearts were assayed by quantitative reverse transcription-PCR and immunohistology with a confocal microscope at 1, 2, 3, 4 and 12 weeks after UTMD. Exogenous TB4 stimulation resulted in the presence of WT1-positive cardiac progenitor cells from epicardium to endocardium. TB4 stimulated angiogenesis and arteriogenesis. One month after TB4 gene therapy by UTMD, the percentage of NKX2.5-positive cardiomyocytes was 5.5±1.0% and NKX2.5 mRNA was 24-fold higher than in the control groups (P<0.001). Similar results were found for ISL-1, BrDu, Ki-67, PHH3 and aurora B (P<0.001). Cardiac-specific delivery of exogenous human TB4 gene efficiently stimulates proliferation and differentiation of resident WT1-positive adult cardiac progenitor cells into three intact cardiac cell lineages-vascular endothelial cells, coronary artery smooth muscle cells and cardiac muscle cells in normal adult rat heart.Gene Therapy advance online publication, 15 November 2012; doi:10.1038/gt.2012.89. |
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Authors:
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S Chen; M Shimoda; J Chen; P A Grayburn |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-15 |
Journal Detail:
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Title: Gene therapy Volume: - ISSN: 1476-5462 ISO Abbreviation: Gene Ther. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421525 Medline TA: Gene Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Baylor Research Institute, Dallas, TX, USA. |
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