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Scaffold-based and scaffold-free cardiac constructs for drug testing

発表形態:
総説
主要業績:
主要業績
単著・共著:
共著
発表年月:
2021年07月
DOI:
10.1088/1758-5090/ac1257
会議属性:
指定なし
査読:
有り
リンク情報:

日本語フィールド

著者:
*Kenichi Arai, Takahiro Kitsuka, Koichi Nakayama
題名:
Scaffold-based and scaffold-free cardiac constructs for drug testing
発表情報:
Biofabrication 巻: 13 号: 4
キーワード:
animal testing; cardiomyocyte; induced pluripotent stem cell; tissue engineering
概要:
The safety and therapeutic efficacy of new drugs are tested in experimental animals. However, besides being a laborious, costly process, differences in drug responses between humans and other animals and potential cardiac adverse effects lead to the discontinued development of new drugs. Thus, alternative approaches to animal tests are needed. Cardiotoxicity and responses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to drugs are conventionally evaluated by cell seeding and two-dimensional (2D) culture, which allows measurements of field potential duration and the action potentials of CMs using multielectrode arrays. However, 2D-cultured hiPSC-CMs lack 3D spatial adhesion, and have fewer intercellular and extracellular matrix interactions, as well as different contractile behavior from CMsin vivo. This issue has been addressed using tissue engineering to fabricate three-dimensional (3D) cardiac constructs from hiPSC-CMs culturedin vitro. Tissue engineering can be categorized as scaffold-based and scaffold-free. In scaffold-based tissue engineering, collagen and fibrin gel scaffolds comprise a 3D culture environment in which seeded cells exhibit cardiac-specific functions and drug responses, whereas 3D cardiac constructs fabricated by tissue engineering without a scaffold have high cell density and form intercellular interactions. This review summarizes the characteristics of scaffold-based and scaffold-free cardiac tissue engineering and discusses the applications of fabricated cardiac constructs to drug screening.
抄録:

英語フィールド

Author:
*Kenichi Arai, Takahiro Kitsuka, Koichi Nakayama
Title:
Scaffold-based and scaffold-free cardiac constructs for drug testing
Announcement information:
Biofabrication Vol: 13 Issue: 4
Keyword:
animal testing; cardiomyocyte; induced pluripotent stem cell; tissue engineering
An abstract:
The safety and therapeutic efficacy of new drugs are tested in experimental animals. However, besides being a laborious, costly process, differences in drug responses between humans and other animals and potential cardiac adverse effects lead to the discontinued development of new drugs. Thus, alternative approaches to animal tests are needed. Cardiotoxicity and responses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to drugs are conventionally evaluated by cell seeding and two-dimensional (2D) culture, which allows measurements of field potential duration and the action potentials of CMs using multielectrode arrays. However, 2D-cultured hiPSC-CMs lack 3D spatial adhesion, and have fewer intercellular and extracellular matrix interactions, as well as different contractile behavior from CMsin vivo. This issue has been addressed using tissue engineering to fabricate three-dimensional (3D) cardiac constructs from hiPSC-CMs culturedin vitro. Tissue engineering can be categorized as scaffold-based and scaffold-free. In scaffold-based tissue engineering, collagen and fibrin gel scaffolds comprise a 3D culture environment in which seeded cells exhibit cardiac-specific functions and drug responses, whereas 3D cardiac constructs fabricated by tissue engineering without a scaffold have high cell density and form intercellular interactions. This review summarizes the characteristics of scaffold-based and scaffold-free cardiac tissue engineering and discusses the applications of fabricated cardiac constructs to drug screening.


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