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- Title
Stimulation of adult resident cardiac progenitor cells by durable myocardial expression of thymosin beta 4 with ultrasound-targeted microbubble delivery.
- Authors
Chen, S; Shimoda, M; Chen, J; Grayburn, P A
- Abstract
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.
- Subjects
PROGENITOR cells; HEART cells; THYMOSIN; MICROBUBBLES; GENE therapy; ULTRASONIC imaging; TRANSPOSONS; REVERSE transcriptase polymerase chain reaction; IMMUNOHISTOCHEMISTRY; NEOVASCULARIZATION
- Publication
Gene Therapy, 2013, Vol 20, Issue 2, p225
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/gt.2012.89