Abstract 2671: Effects Of Adult Progenitor Cell Transplantation On Unitary Sarcoplasmic Reticulum Calcium Release Events In Failing Recipient Cardiomyocytes
Cell transplantation can enhance ventricular function in heart failure, but the underlying mechanisms responsible remain unknown. We have previously shown that bone marrow mononuclear cells (BM) and skeletal myoblasts (SK) restore recipient cardiomyocyte contractile function, possibly through soluble mediators. In this study we tested the hypothesis that calcium release properties of the sarcoplasmic reticulum (SR) may be a target of cell transplantation and a cause for improved cell function, as SR calcium regulation has a central role in the pathophysiology of heart failure. Myocardial infarction was induced in adult Sprague-Dawley rats by left coronary artery ligation (HF). Left ventricular ejection fraction after 3 weeks was 28 ± 1.3%  (mean ± SEM [n]). BM or SK were injected into the heart by intramuscular route. After 4 weeks, recipient cardiomyocytes were isolated and loaded with the calcium-sensitive dye fluo-4 AM. SR calcium release properties were studied by monitoring calcium sparks (CaSp) and waves using confocal microscopy. CaSp frequency was increased in HF compared to Sham while failing cardiomyocytes from the BM or SK group were not (CaSp/100 μm/s: Sham = 0.95 ± 0.14 ; HF = 1.95 ± 0.28 , p < 0.05; BM = 1.42 ± 0.23 ; SK = 1.28 ± 0.18 ). There was an increase in CaSp width in HF which was also present in BM group (width at half-maximal (μm): Sham = 2.89 ± 0.04 ; HF = 3.13 ± 0.04 , p < 0.001; BM = 3.03 ± 0.03 , p < 0.05; SK = 2.99 ± 0.03 ). CaSp duration was reduced in the SK group compared with Sham (duration at half-maximal (μs): Sham = 20.4 ± 0.83 ; HF = 20.39 ± 0.45 ; BM = 18.74 ± 0.4 ; SK = 18.14 ± 0.4 , p < 0.05). HF increased the incidence of calcium waves compared with Sham (events/s: HF 0.056 ± 0.01, ; Sham 0.02 ± 0.006 , p < 0.01). Cardiomyocytes from failing hearts injected with either BM or SK had significantly lower rate of calcium waves compared with HF (events/s: BM 0.016 ± 0.005 , p < 0.01; and SK 0.03 ± 0.008 , p< 0.05). These findings suggest that transplanted cells, possibly by paracrine mechanisms, can influence the behaviour of calcium regulation and release at the level of the ryanodine receptor. This could be important in improving recipient myocyte function after cell transplantation.