SASAKI Daisuke    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Assistant Professor (Fixed Term)
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Measuring the contractile force of multilayered human cardiac cell sheets.
Journal	Formal name：Tissue engineering. Part C, Methods. Abbreviation：Tissue Eng Part C Methods ISSN code：19373384/19373392
Domestic / Foregin	Foregin
Volume, Issue, Page	26(9),pp.485-492
Author and coauthor	SAKAGUCHI Katsuhisa†, TAKAHASHI Hiroaki, TOBE Yusuke, SASAKI Daisuke, MATSUURA Katsuhisa, IWASAKI Kiyotaka, SHIMIZU Tatsuya*, UMEZU Mitsuo
Publication date	2020/09/17
Summary	Three-dimensional (3D) cardiac tissue reconstruction using tissue engineering technology is a rapidly growing area of regenerative medicine and drug screening model development. Our laboratory has developed a novel drug screening model that measures the contractile force of cardiac cell sheets prepared using temperature-responsive culture dishes. There is an urgent need to measure the contractile force of 3D myocardial tissue close to the living body to accurately predict the drug sensitivity of human heart tissue. However, as difficulties arise during the stacking of cardiomyocyte sheets, the effect of stacking on the contractile force is unknown. We therefore established a method of stacking cell sheets using centrifugal force, making it possible to measure 3D myocardial tissue. Human iPS cell-derived cardiomyocytes were seeded in a temperature-responsive culture dish and processed into a sheet. The cardiac cell sheets were multilayered to construct 3D cardiac tissue. The contractile force and cross-sectional area of the multilayered 3D cardiac tissue were measured, and these measurements were used to determine the relationship between the cross-sectional area of the cardiac tissue and its contractile force. The contractile force of the 1-, 3-, and 5-layer tissues increased linearly in proportion to the cross-sectional area. A result of 6.4 mN/mm2, which is one-seventh of the contractile force found in adult tissue, was obtained. However, with 7-layer tissues, there was a sudden drop in the contractile force, possibly due to limited oxygen and nutrient supply. In conclusion, we established a method wherein the thickness of the cell sheets was controlled via layering, thus enabling accurate evaluation of the cardiac contractile function. This method may enable comparisons to living heart tissue and can provide information applicable to regenerative medicine and drug screening models.
DOI	10.1089/ten.TEC.2020.0164
PMID	32799760