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Mechanical Measurement and Stimulation of Human Pluripotent Stem Cell-Derived Cardiomyocytes.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Mechanical Measurement and Stimulation of Human Pluripotent Stem Cell-Derived Cardiomyocytes./
作者:
Dou, Wenkun.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:
138 p.
附註:
Source: Dissertations Abstracts International, Volume: 83-06, Section: B.
Contained By:
Dissertations Abstracts International83-06B.
標題:
Biomedical engineering. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28771110
ISBN:
9798496547727
Mechanical Measurement and Stimulation of Human Pluripotent Stem Cell-Derived Cardiomyocytes.
Dou, Wenkun.
Mechanical Measurement and Stimulation of Human Pluripotent Stem Cell-Derived Cardiomyocytes.
- Ann Arbor : ProQuest Dissertations & Theses, 2021 - 138 p.
Source: Dissertations Abstracts International, Volume: 83-06, Section: B.
Thesis (Ph.D.)--University of Toronto (Canada), 2021.
This item must not be sold to any third party vendors.
The emerging heart-on-a-chip platforms are promising approaches to establish cardiac cell/tissue models in vitro for studying cardiac physiologies, disease modeling, cardiotoxicity testing, and therapeutic discoveries. Challenges still exist in realizing the capability of sensing and evaluating the functional properties of cardiac cell/tissue models in situ (i.e., on the platforms). In particular, generating sufficient forces of contraction during the rhythmic beating of cardiomyocytes plays a central role in pumping oxygen-rich blood through the circulatory system. Developing new platforms and technologies to assess the beating behaviors and contractile functions of in vitro cardiac models is essential to provide information on cell/tissue physiologies, drug-induced inotropic responses, and mechanisms of cardiac diseases.This thesis focuses on developing biosensing technologies/platforms for the measurement of contractile functions of in vitro cardiac models. In vitro cardiac cell/tissue models were established by using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (iPSC-CMs) generated with the human proteome to avoid the potential species-dependent differences. Firstly, a label-free imaging technique was developed to offer a cytotoxic-free method for long-term measurement of dynamic beating trajectories, beating amplitude, beating propagation, and conduction velocities of cardiomyocyte monolayers, avoiding the perturbation and cytotoxicity induced by fluorescent dyes. Next, a carbon-based biosensing platform integrated with flexible biosensing components was developed for continuous measurement of multiple parameters of cardiac functional properties in vitro, including contractility, beating rate, beating rhythm, and field potential. In addition, a microdevice array integrated both contraction sensing and mechanical stimulation functions was also developed to recapitulate the mechanical microenvironment of myocardium in vitro and characterize the effect of mechanical strain magnitude on the maturation of iPSC-CMs.Highlighted applications and discoveries enabled by these developed platforms were summarized and discussed in aspects of investigating fundamental cardiac physiologies (e.g., iPSC-CM maturation under mechanical stimulation), drug testing (e.g., isoproterenol, verapamil, blebbistatin, and E-4031), and disease modeling (e.g., drug-induced cardiac arrhythmia and arrhythmogenic right ventricular cardiomyopathy (ARVC)).
ISBN: 9798496547727Subjects--Topical Terms:
535387
Biomedical engineering.
Subjects--Index Terms:
Biosensing platform
Mechanical Measurement and Stimulation of Human Pluripotent Stem Cell-Derived Cardiomyocytes.
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The emerging heart-on-a-chip platforms are promising approaches to establish cardiac cell/tissue models in vitro for studying cardiac physiologies, disease modeling, cardiotoxicity testing, and therapeutic discoveries. Challenges still exist in realizing the capability of sensing and evaluating the functional properties of cardiac cell/tissue models in situ (i.e., on the platforms). In particular, generating sufficient forces of contraction during the rhythmic beating of cardiomyocytes plays a central role in pumping oxygen-rich blood through the circulatory system. Developing new platforms and technologies to assess the beating behaviors and contractile functions of in vitro cardiac models is essential to provide information on cell/tissue physiologies, drug-induced inotropic responses, and mechanisms of cardiac diseases.This thesis focuses on developing biosensing technologies/platforms for the measurement of contractile functions of in vitro cardiac models. In vitro cardiac cell/tissue models were established by using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (iPSC-CMs) generated with the human proteome to avoid the potential species-dependent differences. Firstly, a label-free imaging technique was developed to offer a cytotoxic-free method for long-term measurement of dynamic beating trajectories, beating amplitude, beating propagation, and conduction velocities of cardiomyocyte monolayers, avoiding the perturbation and cytotoxicity induced by fluorescent dyes. Next, a carbon-based biosensing platform integrated with flexible biosensing components was developed for continuous measurement of multiple parameters of cardiac functional properties in vitro, including contractility, beating rate, beating rhythm, and field potential. In addition, a microdevice array integrated both contraction sensing and mechanical stimulation functions was also developed to recapitulate the mechanical microenvironment of myocardium in vitro and characterize the effect of mechanical strain magnitude on the maturation of iPSC-CMs.Highlighted applications and discoveries enabled by these developed platforms were summarized and discussed in aspects of investigating fundamental cardiac physiologies (e.g., iPSC-CM maturation under mechanical stimulation), drug testing (e.g., isoproterenol, verapamil, blebbistatin, and E-4031), and disease modeling (e.g., drug-induced cardiac arrhythmia and arrhythmogenic right ventricular cardiomyopathy (ARVC)).
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