Transplantation of pig iPSC-derived cardiac cells in a pig model of myocardial infarction

• Grant number: 14/14086-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2015
• End date: March 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: José Eduardo Krieger
• Grantee: Clara Steichen
• 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 research grant: 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther, AP.TEM

Abstract

Induced pluripotent stem cells (iPSCs) hold great promise for cell therapy including for replacing damaged cardiomyocytes after a myocardial infarction. However, preclinical studies should be performed to evaluate the feasibility, safety and efficiency of this approach. The aim of this project is to test the hypothesis that transplantation of pig iPSC-derived cardiac cells prevents deterioration of the cardiac function post myocardial infarction in pigs. The major limitation in the use of pig iPSCs for translational cardiac cell therapy studies is the inefficiency of the differentiation of these cells into cardiomycoytes. Based on a strong laboratory expertise on pig iPSC generation, characterization and human cardiomyocyte differentiation, the first specific aims will be the enhancement of pig cardiomyocyte differentiation protocol and the generation of pig iPSC-derived cells which are non-fully differentiated but cardiac committed cells, which we speculate would be the most suitable for transplantation. We plan to test 3D culture systems to increase the potential of pig cells before transplantation and to transplant the cells into a pig model of closed-artery catheter-based myocardial infarction developed in the laboratory. This work would be of significant interest to the field and help for the acceleration of the transition of iPSC-based cell therapy for cardiac regeneration from bench to clinics. (AU)

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; CRAJOINAS, RENATO O.; JENSEN, LEONARDO; DIMA, LENO L.; BURDEYRON, PERRINE; HAUET, THIERRY; GIRAUD, SEBASTIEN; STEICHEN, CLARA. A Sodium Oxalate-Rich Diet Induces Chronic Kidney Disease and Cardiac Dysfunction in Rats. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 17, SEP 2021. (14/14086-7)

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)