Morphological and functional characterization of human induced pluripotent stem cells derived cardiomyocytes after electrical stimulation

• Grant number: 18/16860-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 26, 2018
• End date: November 25, 2019
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Eduardo Krieger
• Grantee: Thayane Antoniolli Crestani
• Supervisor: Elisabeth Ehler
• 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: King's College London, England
• Associated to the scholarship: 16/11321-0 - Mechanical stimulus as a key component for maturation and characterization of human induced pluripotent stem cell-derived cardiomyocytes., BP.DR

Abstract

Fibrous tissue replaces cardiomyocyte following an acute myocardial infarction (AMI) contributing to cardiac remodeling and compromising the organ's contractile capacity. To counteract these effects several gene/cell therapy approaches have been explored in the last decade with poor results. Recently, the use of human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) appears as a promising strategy to restore cardiac function. Although preliminary evidence indicates that iPSC-CMs can engraft and improve cardiac function, this response is accompanied by arrhythmia, which can be a life-threatening condition. The arrhythmia can be explained by poor coupling between the cells or excessive specialized conductive cardiomyocytes indicating that we need to better understand the queues driving the maturation of cardiac cells to specialized conductive tissue or working cardiomyocytes. The objective of this work is to investigate the role of electrical stimulus (ES) during the differentiation and maturation process of iPSC-CMs. We want to characterize the morphological and functional parameters during the differentiation of hiPSCs from cells isolated from urine and fibroblasts of healthy individuals. These cells will be phenotypically characterized according their morphology (shape; myofibrillar maturity; intercalated disc composition) and functional parameters (intracellular Ca2+ transients and action potential). Understanding of the electrical influence may impact the differention process to obtain predominantly iPSC-CM of the specialized conductive system, which is essential to increase the efficiency to derive cells for therapeutic purposes or disease modeling.

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)

CRESTANI, THAYANE; STEICHEN, CLARA; NERI, ELIDA; RODRIGUES, MARILIZA; FONSECA-ALANIZ, MIRIAM HELENA; ORMROD, BETH; HOLT, MARK R.; PANDEY, PRAGATI; HARDING, SIAN; EHLER, ELISABETH; et al. Electrical stimulation applied during differentiation drives the hiPSC-CMs towards a mature cardiac conduction-like cells. Biochemical and Biophysical Research Communications, v. 533, n. 3, p. 376-382, DEC 10 2020. (13/17368-0, 16/11321-0, 14/14086-7, 18/16860-2, 15/50216-5)