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Stimulation of adult resident cardiac progenitor cells by durable myocardial expression of thymosin beta 4 with ultrasound-targeted microbubble delivery

Gene Therapy volume 20, pages 225–233 (2013)Cite this article

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A Corrigendum to this article was published on 06 December 2012

This article has been updated

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.

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  • 07 February 2013

    This article has been corrected since online publication and a corrigendum is also printed in this issue

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Authors and Affiliations

  1. Baylor Research Institute, Dallas, TX, USA

    S Chen, M Shimoda, J Chen & P A Grayburn

  2. Department of Internal Medicine, Division of Cardiology, Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA

    P A Grayburn

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  1. S Chen
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Correspondence to P A Grayburn.

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Chen, S., Shimoda, M., Chen, J. et al. Stimulation of adult resident cardiac progenitor cells by durable myocardial expression of thymosin beta 4 with ultrasound-targeted microbubble delivery. Gene Ther 20, 225–233 (2013). https://doi.org/10.1038/gt.2012.89

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