Induced pluripotent stem cells to study cardiomyocytes derived from patients with genetic cardiomyopathies

Author(s)

Diogo Gonçalves Biagi dos Santos

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2015-05-27

Examining board members

Jose Eduardo Krieger; Lygia da Veiga Pereira Carramaschi; Alexander Augusto de Lima Jorge; Francisco Rafael Martins Laurindo; Karina Griesi Oliveira

• Advisor: Jose Eduardo Krieger

Abstract

The study of genetic mutations as the cause of cardiomyopathies initiates with the discovery of mutations in sarcomeric proteins genes that lead to Hypertrophic Cardiomyopathy. Since then, mutations in several genes, coding to sarcomeric proteins or not, were discovered and listed as the reason to the cardiomyopathies. To study the effect of these mutations was a challenge due the difficulty to accesses cardiac cells. In 2007, the technique of reprogramming somatic cells into pluripotent stem cells was discovered. The fact that the pluripotent stem cells are capable of differentiating into cardiomyocytes opened the opportunity to study these cells from individuals with genetic mutations. This thesis aimed to create a cellular model to study Hypertrophic Cardiomyopathy caused by genetic mutations. Initially we established a cell reprogramming protocol to establish induced stem cells lines from a patient with mutation in MYH7 gene. Having characterized the cells, they were differentiated into cardiomyocytes using an adapted protocol from direct differentiation protocols. Cardiomyocytes generated showed molecular and functional characteristics similar to human primary cardiomyocytes and were visualized by means of transmission electron microscopy. The patient\'s cardiomyocytes had a large proportion of disorganized sarcomeres compared to cardiomyocytes from healthy individuals. In conclusion, the cell model developed suggests that it is possible to study the effect of genetic mutation in Hypertrophic Cardiomyopathy using induced pluripotent stem cells derived cardiomyocytes. (AU)

• FAPESP's process: 10/13426-8 - iPS cells as disease models for inherited cardiomyopathies
• Grantee: Diogo Gonçalves Biagi dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate