Engineering microenvironment for human cardiac tissue assembly in heart-on-a-chip platform

Autor: Ericka J. Knee-Walden, Benjamin F.L. Lai, Milica Radisic, Nicole Feric, Naimeh Rafatian, Yimu Zhao, Peter H. Backx, Erika Yan Wang
Rok vydání: 2020
Předmět:
Zdroj: Matrix Biol
ISSN: 0945-053X
Popis: Organ-on-a-chip systems have the potential to revolutionize drug screening and disease modeling through the use of human stem cell-derived cardiomyocytes. The predictive power of these tissue models critically depends on the functional assembly and maturation of human cells that are used as building blocks for organ-on-a-chip systems. To resemble a more adult-like phenotype on these heart-on-a-chip systems, the surrounding micro-environment of individual cardiomyocyte needs to be controlled. Herein, we investigated the impact of four microenvironmental cues: cell seeding density, types and percentages of non-myocyte populations, the types of hydrogels used for tissue inoculation and the electrical conditioning regimes on the structural and functional assembly of human pluripotent stem cell-derived cardiac tissues. Utilizing a novel, plastic and open-access heart-on-a-chip system that is capable of continuous non-invasive monitoring of tissue contractions, we were able to study how different micro-environmental cues affect the assembly of the cardiomyocytes into a functional cardiac tissue. We have defined conditions that resulted in tissues exhibiting hallmarks of the mature human myocardium, such as positive force-frequency relationship and post-rest potentiation.
Databáze: OpenAIRE
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