Growing human cardiomyocytes in a dish

Just over 15 years ago, the first induced pluripotent stem cells (iPSCs) were generated using mouse fibroblasts ¹. Shortly after, induction of pluripotency in human fibroblasts was also proven possible ², opening a whole new chapter of human based research paradigms. 

Concurrent refinement of differentiation protocols paved the way for cell types such as iPSC-derived cardiomyocytes (iPSC-CMs) to routinely serve as disease models, platforms for drug testing, and enter clinical trials for cell therapies ^3-5.  

However, iPSC-CMs still resemble an embryonic phenotype compared to adult cardiomyocytes, leaving maturation as one of the most pressing challenges in the field. Approaches aiming to mimic biochemical and -mechanical cues that drive heart development in vivo have shown success in approximating the adult cardiac cellular phenotype. Methods such as applying electromechanical stimuli, modifying extracellular matrix, introducing nanotopology, 3D culture and adjusting medium composition also lead to a certain extent of structural and functional maturity, however, several limitations persist ^{6, 7}.  

As part of my project, I will be working on testing various platforms promoting iPSC-CM maturation with compatibility to high throughput screening. 

References:

1. Takahashi, K. and S. Yamanaka, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006. 126(4): p. 663-76. 
2. Takahashi, K., et al., Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 2007. 131(5): p. 861-72. 
3. Lian, X., et al., Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci U S A, 2012. 109(27): p. E1848-57. 
4. Burridge, P.W., et al., Chemically defined generation of human cardiomyocytes. Nat Methods, 2014. 11(8): p. 855-60. 
5. Elliott, D.A., et al., NKX2-5(eGFP/w) hESCs for isolation of human cardiac progenitors and cardiomyocytes. Nat Methods, 2011. 8(12): p. 1037-40. 
6. Ahmed, R.E., et al., A Brief Review of Current Maturation Methods for Human Induced Pluripotent Stem Cells-Derived Cardiomyocytes. Front Cell Dev Biol, 2020. 8: p. 178. 
7. Karbassi, E., et al., Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine. Nature reviews. Cardiology, 2020. 17(6): p. 341-359.