Action potential and Calcium transient phenotyping of cardiomyocytes derived from pluripotent stem cells: development of an electrophysiological platform CM-PSCs compatible to study disease and drug modeling and cardiac regeneration approaches

• Grant number: 16/07541-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: September 30, 2016
• End date: September 29, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Eduardo Krieger
• Grantee: Rafael Dariolli
• Supervisor: Eric Anthony Sobie
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Icahn School of Medicine at Mount Sinai, United States
• Associated to the scholarship: 14/24577-8 - Nanostructures and iPSC derived cardiomyocytes approaches for cardiac protection and repair post-MI, BP.PD

Abstract

Cardiovascular diseases are the leading causes of death worldwide, especially myocardial infarction (MI). In this context, the use of stem cells aiming cardiomyoplasty has been shown a promising approach. However, adult stem cells have proved inefficiency to provide regeneration of injured myocardium. Induced pluripotent stem cells (iPSCs) hold great promise for cell therapy after MI and also new designs to study disease modeling and drug tests. Thus, to obtain singular improvements in cardiac regeneration and valuable information to cellular models of diseases and drugs design, the electrophysiology of pluripotent derived cardiac cells (CM-PSCs) should be better understood. CM-PSCs are a very specific type of contractile cells based in their maturation levels and type of differentiation protocol used to differentiate them. Actually, almost all the methods used to study electrophysiology in CM-PSCs were built based on adult cardiac contractile cells imposing huge limitation to data analysis and interpretation. So, to develop specific electrophysiological platforms able to study CM-PSCs very advanced knowledge should be implemented. In this context, Dr's Sobie team from Icahn School of Medicine at Mount Sinai, New York, have been building specialized technology with this propose becoming one of the most specialized groups to develop these approaches worldwide. So, in collaboration with Dr's Sobie lab, the main goal of this proposal is to develop a suitable and reproducible cellular electrophysiological platform to evaluate calcium transients and action potentials of CM-PSCs and validate this platform in a variety of cells from our bank of stem cells from different diseases. The results of this study may contribute to identify the electrophysiological properties of PSCs derived cardiac cells. This proposal is of great interest to accelerate the development of novel alternative or complementary strategies to regenerate the myocardium post-MI and the development of precision medicine approaches.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MUNOZ, JUAN J. A. M.; DARIOLLI, RAFAEL; DA SILVA, CAIO MATEUS; NERI, ELIDA A.; VALADAO, IURI C.; TURACA, LAURO THIAGO; LIMA, VANESSA M.; PERES DE CARVALHO, MARIANA LOMBARDI; VELHO, MARILIZA R.; SOBIE, ERIC A.; et al. Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation. STEM CELL RESEARCH & THERAPY, v. 13, n. 1, p. 27-pg., 2022-09-02. (16/07541-5, 14/50889-7, 13/17368-0, 15/50216-5, 14/24577-8)

ALVES, CHRYSTIAN JUNQUEIRA; DARIOLLI, RAFAEL; HAYDAK, JONATHAN; KANG, SANGJO; HANNAH, THEODORE; WIENER, ROBERT J.; DEFRONZO, STEFANIE; TEJERO, RUT; GUSELLA, GABRIELE L.; RAMAKRISHNAN, AARTHI; et al. Plexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion. NATURE COMMUNICATIONS, v. 12, n. 1, OCT 14 2021. (16/07541-5)