シミズ　タツヤ   SHIMIZU Tatsuya   清水　達也    所属   研究施設 研究施設    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	In vitro circulation model driven by tissue-engineered dome-shaped cardiac tissue.
掲載誌名	正式名：Biofabrication 略　 称：Biofabrication ISSNコード：17585090/17585082
掲載区分	国外
巻・号・頁	14(3),pp.035020
著者・共著者	KIKUCHI Tetsutaro†*, MATSUURA Katsuhisa, SHIMIZU Tatsuya
担当区分	最終著者
発行年月	2022/06/10
概要	The heart is an essential organ for animals and humans. With the increased availability of pluripotent stem cells, the use of three-dimensional cardiac tissues consisting of cultured cardiomyocytes in in vitro drug evaluation has been widely studied. Several models have been proposed for the realization of the pump function, which is the original function of the heart. However, there are no models that simulate the human circulatory system using cultured cardiac tissue. This study shows that a dome-shaped cardiac tissue fabricated using the cell sheet stacking technique can achieve a heart-like pump function and circulate culture medium, there by mimicking the human circulatory system. Firstly, human induced pluripotent stem cells were differentiated into autonomously beating cardiomyocytes, and cardiomyocyte cell sheets were created using temperature-responsive culture dishes. A cardiomyocyte sheet and a human dermal fibroblast sheet were stacked using a cell sheet manipulator. This two-layered cell sheet was then inflated to create a dome-shaped cardiac tissue with a base diameter of 8 mm. The volume of the dome-shaped cardiac tissue changed according to the autonomous beating. The stroke volume increased with the culture period and reached 21 ± 8.9 μL (n = 6) on day 21. It also responded to β-stimulant and extracellular calcium concentrations. Internal pressure fluctuations were also recorded under isovolumetric conditions by dedicated culture devices. The peak heights of pulsatile pressure were 0.33 ± 0.048 mmHg (n = 3) under a basal pressure of 0.5 mmHg on day 19. When the tissue was connected to a flow path that had check valves applied, it drove a directional flow with an average flow rate of approximately 1 μL/s.
DOI	10.1088/1758-5090/ac77c1
PMID	35688123