PT  - JOURNAL ARTICLE
AU  - Carr, C A
AU  - Carpenter, L
AU  - Yang, C T
AU  - Stuckey, D J
AU  - Clarke, K
AU  - Watt, S M
TI  - 15 Efficient cardiac differentiation of human induced pluripotent stem cells, that engraft and protect against ischaemic damage in the infarcted rat heart
AID  - 10.1136/heartjnl-2011-300920b.15
DP  - 2011 Oct 15
TA  - Heart
PG  - e7--e7
VI  - 97
IP  - 20
4099  - http://heart.bmj.com/content/97/20/e7.14.short
4100  - http://heart.bmj.com/content/97/20/e7.14.full
SO  - Heart2011 Oct 15; 97
AB  - Induced pluripotent stem (iPS) cells provide a promising source of cardiac progenitor cells for administration to the infarcted heart. Here, we describe a protocol for efficient, serum free, directed differentiation of human iPS cells, as a monolayer, that yields a mixed population in which cardiomyocytes, endothelium and smooth muscle cells constitute over 50% of the differentiated population, with no additional selection strategies utilised. GFP positive cardiac progenitors from human iPS cells (2×106) were administered by direct injection into the myocardium of athymic nude rats following 50 min of ischaemia. Cardiac function was measured using MRI at 2 days, 2, 6 and 10 weeks. At 10 weeks the hearts were removed for histology. By 6 weeks, control infarcted hearts (n=5) had significantly larger end systolic volumes and lower ejection fractions than sham operated hearts (n=3) whereas hearts treated with iPS-derived cardiac differentiated cells (n=4) maintained cardiac function; such that by 10 weeks the end systolic volumes and ejection fractions were not significantly different from those of the sham operated animals (ejection fraction at 10 weeks: sham 77±5%, infarct 45±9% (p<0.05 vs sham), iPS 62±4%). Histological analysis showed that the human iPS-derived cardiac progenitor cells engrafted, differentiated into cardiomyocytes and smooth muscle, and persisted for at least 10 weeks post-infarct. Thus efficient directed differentiation of human iPS cells towards the cardiac lineage generates cells that can prevent loss of heart function after ischaemic heart damage.