Sabrina Bech Mathiesen - Postdoctoral Fellowship 2021
Project summary:
Maturing induced pluripotent stem cell derived cardiomyocytes for heart repair
The heart is unable to replace dead heart muscle cells (CMs) lost to injury. However, recent advances in generating CMs from induced pluripotent stem cells (iPSC-CMs) has given hope for a feasible therapy to replenish the lost CMs. Yet, current iPSC-CMs resemble fetal more than adult CMs and this immaturity remains a challenge. This project aims to mature iPSC-CMs to create more competent cells for patients by mimicking physiological oxygen tensions during development and by adjusting gene expression to favor maturity.
Project Title
Maturation of induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) for heart repair
Background
iPSC-CMs are a promising source of therapeutical CMs and can to some extent integrate into the myocardium of small and large mammals, including primates. However, major concerns still remain regarding immaturity of the engrafted CMs, which increases the susceptibility for arrythmias immediately upon transplantation. Furthermore, injected iPSC-CMs exhibit a maturation process of months duration, reflecting suboptimal derivation protocols.
Aim
We seek to improve iPSC-CM maturation and hereby facilitate their clinical translation. In specific, we will mimic continuous physiological oxygen tensions during iPSC-CM cultivation as experienced during cardiac development. Furthermore, we will exploit a novel set of transcription factors (TFs) identified in our recent unique single cell RNA sequencing dataset of in vivo sorted CMs, and by virus transduction test the TFs ability to improve iPSC-CM maturation.
Methods
- Induced pluripotent stem cell (iPSC) culturing in a highly controlled environment (humidity, ideal gas (O2/CO2) and temperature) in our GMP facility
- Deriving CMs from iPSC
- Single cell RNA sequencing (scRNAseq)
- Adeno associated virus 9 (AAV9) mediated gene expression
- Immunocytochemistry
- Flow cytometry
- Patch Clamp
- qPCR
- Contractility assays
- Confocal and electron microscopy
Sabrina Bech Mathiesen
- MSc in Molecular Biology and PhD
- University of Southern Denmark, Clinical Institute
Mentors:
Professor Ditte Caroline Andersen, Clinical Institute, University of Southern Denmark
Partners:
-
Assistant Professor Ellen Ngar-Yun Poon, Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong
- Assistant Professor David Zebrowski, Department of Medicine & Therapeutics, Center for Cardiovascular Genomics and Medicine
Faculty of Medicine, The Chinese University of Hong Kong