Mechanical stimulus as a key component for maturation and characterization of human induced pluripotent stem cell-derived cardiomyocytes.

• Grant number: 16/11321-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2017
• End date: October 31, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Eduardo Krieger
• Grantee: Thayane Antoniolli Crestani
• 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
• Associated scholarship(s): 18/16860-2 - Morphological and functional characterization of human induced pluripotent stem cells derived cardiomyocytes after electrical stimulation, BE.EP.DR

Abstract

After an acute myocardial infarction (AMI), cardiomyocytes (CMs) are eliminated and replaced by fibrous tissue displaying poor contractile capacity. The use of human induced pluripotent stem cells (hiPSCs) is a promising strategy to restore cardiac function, as these cells are able to differentiate into various cell types, such as CMs (hiPSC-CMs). However, the complete characterization of cells generated during differentiation as well as the choice of the optimal cell population to use for cardiac repair need to be further assessed. The objectives of this work are: 1) to test the hypothesis that mechanical stimulus could play a role during differentiation process or influence maturation status of hiPSC-CMs; 2) to determine if mechanical properties and calcium transient are critical parameters in the determination of the best hiPSC-CMs phenotype to use for therapeutic strategies or disease modeling. hiPSCs will be reprogrammed from cells isolated from urine of healthy individuals and patients from Instituto do Coração. These cells will be mechanically stimulated during their guided differentiation in CMs and phenotypically characterized by molecular/cell parameters and the proposed functional parameters (mechanical properties and calcium transient). This work can help increase the understanding and efficiency of the differentiation process of hiPSCs into the cardiac lineage, and contribute in the identification of the best functional parameters to test iPSC-CMs for both therapeutic purposes (after AMI, for example) and disease modeling for cardiac genetic disorders (hypertrophic cardiomyopathy, for instance).

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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CRESTANI, Thayane Antoniolli. Electrical stimulation applied during hiPSC differentiation drives the hiPSC-CMs towards a mature cardiac conduction-like cells. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.