Abstract
Cardiomyocytes differentiated from pluripotent stem cells (PSC-CMs) hold a great potential for the study and the cure of cardiovascular disease; indeed they have been largely used as platform for disease modeling and drugs testing, and represent a promising source of cells for regenerative therapies. However, their immature phenotype represents a major hurdle for their full application; indeed, PSC-CMs differ from adult ones for molecular, metabolic and morpho-functional properties. Recently, a new technology based on optical excitation of organic semiconductors (OS) has been shown to be able to modulate the behavior of many cell types by targeting different cellular processes, as proliferation, angiogenesis and calcium signalling. Here, we adopted a multidisciplinary approach based on morpho-functional, metabolic and transcriptional analyses to study the effect of OS-photoexcitation on PSC-CMs, by the use of a red-light sensitive OS polymer, namely Poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-b']dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT), in the form of a thin film. Our results revealed a significant modulation of markers of maturation in PSC-CMs exposed to PCPDTBT and photomodulation, showing increased size, a shift of their maximal diastolic potential toward more negative values, and augmented Ca 2+ transient amplitude. Moreover, by Scanning ElectroChemical Microscopy (SECM) we found a decrease in glucose uptake and lactate release upon PCPDTBT light stimulation, potentially indicating a switch toward a more adult-like metabolism in stimulated PSC-CMs. Recently obtained RNA sequencing data are in line with these results, and will provide us with hints on the underlying molecular mechanisms. In conclusion, although not definitive, our data are in support of a potential effect of polymer-mediated optical photoexcitation in boosting PSC-CMs toward a more mature phenotype. The demonstration of a relevant effect of OS-photomodulation on PSC-CM maturation and functionality will significantly promote their full applications toward personalized medicine.This research was supported by EU Horizon 2020 FETOPEN- 2018-2020 Programme ‘LION- HEARTED’-GA #828984
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