Novel High-throughput Drug Screening Application Using Human Cardiomyocytes In Mechanically Controlled Environment
Year: 2019
Type: dissertation
Abstract: Drug side-effects endanger patients and cause drug recalls from the market. High-throughput screening (HTS) tests with human cardiomyocytes (CMs) can detect drug side-effects earlier in the drug development process, but no available HTS test assesses CM contraction amplitude. We established 96-well substrates with modulus corresponding to both, healthy and diseased heart tissue that ‘wrinkle’ upon cell force exertion. Stem cell-derived CMs were used to quantify frequency, amplitude, and regularity of contraction in response to substrate modulus, drugs with known effects on heart function, and electrical pacing. The wrinkling device was benchmarked against an industry-standard impedance assay. Wrinkling substrates tuned to the modulus of heart enhanced CM maturity, including sarcomere alignment (α-actinin staining), which correlated with higher degree of CM responsiveness to drug treatment. Thus, the wrinkling assay fills the gap of HTS tests for the measure of CM contraction amplitude and enhances the sensitivity of in vitro drug tests.
Source: TSpace (University of Toronto)
Author: Gyutae Kim
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3196049316