In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. suppl_2 ( 2014-11-25)
Abstract:
BACKGROUNDS: Previously we reported beneficial effects of transplantation of all mouse ES cell-derived cardiac cell sheets composed of CMs and vascular cells (endothelial cells [ECs]/ vascular mural cells [MCs] ) in a rat myocardial infarction (MI) model and importance of co-existence of vascular cells in the cell sheets (Stem Cells, 2012). Here we report a transplantation of human induced pluripotent stem cell (hiPSC)-derived cardiac cells to a porcine MI model. METHODS & RESULTS: We induced a mixture of CMs and vascular cells from hiPSCs with a 2-D serum-free method (modified from Uosaki, PLoS One, 2011). We generated cell sheets using 10cm-sized temperature-responsive culture dishes (UpCell; CellSeed, Tokyo, Japan). Self-pulsating cardiac cell sheets were approximately 3.5cm in diameter with 6.8х106±0.8 (n=5) of cells containing cTnT+-CMs (19.4±5.9%), VE-cadherin+-ECs (3.8±4.4%) and PDGFRβ+-MCs (67.2±7.8%). We induced MI in micromini-pigs (12-45 month old) by ameroid constriction of coronary artery and transplanted cell sheets (Tx) 2 weeks after MI induction (4 sheets / recipient) under immunosuppression. In Tx group, echocardiogram showed a significant improvement of systolic function of left ventricle (fractional shortening: 22.6±5.0 vs 39.7±8.7%, p 〈 0.01, n=5). Ejection fraction evaluated by left ventriculogram improved significantly in Tx group (25.3±6.2% vs 39.8±4.2%, p 〈 0.01, n=5). Speckle tracking echocardiogram showed significant increase of attenuated circumference strain in infarcted and border regions leading to restored dyssynchrony (anterior: 10.8±4.1 vs 20.6±3.5%, p 〈 0.01, antero-lateral: 13±6.5% vs 24.8±7.6%, p 〈 0.05, n=5, 2 weeks after Tx). Capillary density in the border region significantly elevated indicating angiogenic effect of the sheet transplantation (75.9±42.6/mm2 vs 137.4±44.8/mm2, p 〈 0.001, n=5). CONCLUTION: HiPSC-derived cardiac cell sheets potentially ameliorate cardiac dysfunction of human-size infarct heart.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.130.suppl_2.17227
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2014
detail.hit.zdb_id:
1466401-X
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