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Regen Med. 2010 Mar;5(2):231-44. doi: 10.2217/rme.09.83.

Therapeutic angiogenesis by transplantation of human embryonic stem cell-derived CD133+ endothelial progenitor cells for cardiac repair.

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1
Falk Cardiovascular Research Centre, Stanford School of Medicine, USA.

Abstract

OBJECTIVE:

This study aim to enhance endothelial differentiation of human embryonic stem cells (hESCs) by transduction of an adenovirus (Ad) vector expressing hVEGF(165) gene (Ad-hVEGF(165) ). Purified hESC-derived CD133(+) endothelial progenitors were transplanted into a rat myocardial infarct model to assess their ability to contribute to heart regeneration.

METHODS:

Optimal transduction efficiency with high cell viability was achieved by exposing differentiating hESCs to viral particles at a ratio of 1:500 for 4 h on three consecutive days.

RESULTS:

Reverse transcription-PCR analysis showed positive upregulation of VEGF, Ang-1, Flt-1, Tie-2, CD34, CD31, CD133 and Flk-1 gene expression in Ad-hVEGF(165) -transduced cells. Additionally, flow cytometric analysis of CD133, a cell surface marker, revealed an approximately fivefold increase of CD133 marker expression in Ad-hVEGF(165)-transduced cells compared with the nontransduced control. Within a rat myocardial infarct model, transplanted CD133(+) endothelial progenitor cells survived and participated, both actively and passively, in the regeneration of the infarcted myocardium, as seen by an approximately threefold increase in mature blood vessel density (13.62 +/- 1.56 vs 5.11 +/- 1.23; p < 0.01), as well as significantly reduced infarct size (28% +/- 8.2% vs 76% +/- 5.6%; p < 0.01) in the transplanted group compared with the culture medium-injected control. There was significant improvement in heart function 6 weeks post-transplantation, as confirmed by regional blood-flow analysis (1.72 +/- 0.612 ml/min/g vs 0.8 +/- 0.256 ml/min/g; p < 0.05), as well as echocardiography assessment of left ventricular ejection fraction (60.855% +/- 7.7% vs 38.22 +/- 8.6%; p < 0.05) and fractional shortening (38.63% +/- 9.3% vs 25.2% +/- 7.11%; p < 0.05).

CONCLUSION:

hESC-derived CD133(+) endothelial progenitor cells can be utilized to regenerate the infarcted heart.

PMID:
20210583
DOI:
10.2217/rme.09.83
[Indexed for MEDLINE]

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