BackgroundInsulin-like growth factor 1 (IGF-1) activates prosurvival pathways and improves postischemic cardiac function, but this key cytokine is not robustly expressed by cultured human cardiac stem cells. We explored the influence of an enhanced IGF-1 paracrine signature on explant-derived cardiac stem cell–mediated cardiac repair.Methods and ResultsReceptor profiling demonstrated that IGF-1 receptor expression was increased in the infarct border zones of experimentally infarcted mice by 1 week after myocardial infarction. Human explant-derived cells underwent somatic gene transfer to overexpress human IGF-1 or the green fluorescent protein reporter alone. After culture in hypoxic reduced-serum media, overexpression of IGF-1 enhanced proliferation and expression of prosurvival transcripts and prosurvival proteins and decreased expression of apoptotic markers in both explant-derived cells and cocultured neonatal rat ventricular cardiomyocytes. Transplant of explant-derived cells genetically engineered to overexpress IGF-1 into immunodeficient mice 1 week after infarction boosted IGF-1 content within infarcted tissue and long-term engraftment of transplanted cells while reducing apoptosis and long-term myocardial scarring.ConclusionsParacrine engineering of explant-derived cells to overexpress IGF-1 provided a targeted means of improving cardiac stem cell–mediated repair by enhancing the long-term survival of transplanted cells and surrounding myocardium.

Simulations of Y PET confirm that quantitativeY is achievable with the same approach as that used for F, and that there is likely very little margin for improvement by attempting to model aspects unique toY, such as the much higher random fraction or the presence of bremsstrahlung in the singles data.

The GATE software platform, based on the Geant4 toolkit for simulating particle interactions with matter, enables simulation of, among other medical imaging and treatment systems, positron emission tomography. However, at least one publication (Moraes et al 2015 Phys. Med. 31 43-8) has reported discrepancies between the expected results and those obtained using GATE simulations, specifically with respect to the coincidence sorter which processes single events detected by the scanner to find coincidence pairs. In particular, the current software appears to overestimate the number of 'true' coincidence pairs when in multi-window mode, while the delayed coincidence window, used to estimate the randoms present in the prompt coincidence window, underestimates the randoms. Both effects are particularly evident at high count rates. We have investigated this discrepancy and reproduced the reported problems. We have also rewritten the relevant portion of the GATE code to correct the issue. In this note we describe the modifications to the coincidence sorter and repeat the simulations which previously showed unexpected results. Some discrepancies remain in the estimation of the randoms with the single-window mode which are a consequence of the algorithm itself. In multi-window mode however, the simulation agrees exactly with the expected results. The modifications to the coincidence sorter code will be incorporated into the next release of GATE (> version 7.2).