Organic Semiconductor photomodulation enhances maturation of PSC-derived cardiomyocytes
Camilla Galli a, Nicolo' Salvarani a, Carlotta Ronchi b, Gabriele Tullii b, Camilla Marzuoli b, Marco Malferrari c, Stefania Rapino c, Maria Rosa Antognazza b, Elisa Di Pasquale a
a Department of Cardiovascular Medicine, Stem Cells Lab, Humanitas Clinical and Research Center – IRCCS, Rozzano (MI) 20089, Italy
b Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, via Pascoli 70/3, 20133 Milano, Italy
c Dipartimento di Chimica "Giacomo Ciamician, Alma Mater Studiorum, Università di Bologna, Via Francesco Selmi, 2, 40126 Bologna, Italy.
Proceedings of Bioelectronic Interfaces: Materials, Devices and Applications (CyBioEl)
Limassol, Cyprus, 2024 October 22nd - 25th
Organizers: Eleni Stavrinidou and Achilleas Savva
Invited Speaker, Maria Rosa Antognazza, presentation 031
Publication date: 28th June 2024

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 extensively used as platform for disease modeling and drugs testing, and represent a promising source of cells for regenerative therapies. However, the immature phenotype of these cells, which differ from adult cardiomyocytes for molecular, metabolic and morpho-functional properties, is a major hurdle for their full application. Recently, a new technology based on optical excitation of light-sensitive organic semiconductors (OS) has been shown to be able to modulate cell behavior of many cell types by targeting different cellular pathways, as proliferation, angiogenesis, neuronal firing and contractility. Here, we adopted a multidisciplinary approach based on morpho-functional, metabolic and transcriptional analyses to investigate the effect of OS-photoexcitation on PSC-CMs. Analyses were performed on PSC-CMs seeded on either glass (control) or a red-light sensitive OS polymer namely Poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-bʹ]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT), in form of a thin film. Our results revealed a significant modulation of markers of CM maturation in PSC-CMs exposed to PCPDTBT and photomodulation, showing an increased size, by means of membrane capacitance, a shift of their maximal diastolic potential (MDP) toward more negative values, and augmented Ca2+ 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.

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