Schoepp 2017 MiPschool Obergurgl
Schoepp T (2017)
Event: MiPschool Obergurgl 2017
Due to the inaccessibility of multiple cells in the human body, like cardiomyocytes (CMs) or neuronal cells (NCs), their in vitro generation is of great interest as it represents a recent option for disease modelling and regenerative medicine. Directed differentiation of human pluripotent stem cells (hPSCs), both embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), is often limited by the low efficiency in generating the desired cell population and the lack of knowledge regarding signalling pathways functioning during human development.
Worldwide, cardiovascular diseases are the number one cause of death. Therefore, the interest in cardiac cells is high and multiple research groups are trying to establish optimal differentiation conditions to maximize the yield of functioning, beating CMs. These cells have been shown to be especially difficult to differentiate and maintain, but recent development-related knowledge helped to establish defined protocols with increased efficiency. However, these protocols should be adapted to different hPSC lines, including patient derived ones.
The aim of this project will be to apply and optimize protocols of hPSC differentiation towards CMs in order to use them for a cellular model of Friedreich’s ataxia (FRDA), a monogenic progressive mitochondrial disease affecting mainly NCs and CMs. It is known that FRDA patients often die from cardiomyopathy.
The goals within my Master’s project are to first apply the protocol of Burridge et al. 2014  to a hESC line and subsequently characterize the obtained cells by morphology and gene expression. Further the CM differentiation protocol will be optimized and applied to FRDA- and control hiPSC lines in order to obtain a homogeneous population of beating CMs for all lines. This will be followed by analyzing of the mitochondrial function in the beating CMs generated from 2 healthy controls and 2 FRDA patient hiPSCs. This will be done using assays for mitochondrial membrane potential, respiration, oxidative stress and cell death.
This project will lead to a better understanding of the human CMs, especially in conjunction with FRDA, and to establishment of a more complex cellular model for FRDA.
• Bioblast editor: Kandolf G
Labels: MiParea: Patients Pathology: Cardiovascular, Neurodegenerative
Organism: Human Tissue;cell: Heart
- Inst Neuroscience, Innsbruck Medical Univ, Austria. - [email protected]
- Burridge PW, Metzler SA, Nakayama KH, Abilez OJ, Simmons CS, Bruce MA, Matsuura Y, Kim P, Wu JC, Butte M, Huang NF, Yang PC (2014) Multi-cellular interactions sustain long-term contractility of human pluripotent stem cell-derived cardiomyocytes. Am J Transl Res 6:724-35.