Excitation propagation in three-dimensional engineered hearts using decellularized extracellular matrix

Haruyo Yasui, Jong Kook Lee, Akira Yoshida, Teruki Yokoyama, Hiroyuki Nakanishi, Keiko Miwa, Atsuhiko T. Naito, Toru Oka, Hiroshi Akazawa, Junichi Nakai, Shigeru Miyagawa, Yoshiki Sawa, Yasushi Sakata, Issei Komuro

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Engineering of three-dimensional (3D) cardiac tissues using decellularized extracellular matrix could be a new technique to create an "organ-like" structure of the heart. To engineer artificial hearts functionally comparable to native hearts, however, much remain to be solved including stable excitation-propagation. To elucidate the points, we examined conduction properties of engineered tissues. We repopulated the decellularized hearts with neonatal rat cardiac cells and then, we observed excitation-propagation of spontaneous beatings using high resolution cameras. We also conducted immunofluorescence staining to examine morphological aspects. Live tissue imaging revealed that GFP-labeled-isolated cardiac cells were migrated into interstitial spaces through extravasation from coronary arteries. Engineered hearts repopulated with Ca2+-indicating protein (GCaMP2)-expressing cardiac cells were subjected to optical imaging experiments. Although the engineered hearts generally showed well-organized stable excitation-propagation, the hearts also demonstrated arrhythmogenic propensity such as disorganized propagation. Immunofluorescence study revealed randomly-mixed alignment of cardiomyocytes, endothelial cells and smooth muscle cells. The recellularized hearts also showed disarray of cardiomyocytes and markedly decreased expression of connexin43. In conclusion, we successfully demonstrated that the recellularized hearts showed dynamic excitation-propagation as a "whole organ". Our strategy could provide prerequisite information to construct a 3D-engineered heart, functionally comparable to the native heart.

Original languageEnglish
Pages (from-to)7839-7850
Number of pages12
Issue number27
Publication statusPublished - 2014 Sept


  • Cardiac tissue engineering
  • ECM (extracellular matrix)
  • Electrophysiology
  • Organ culture
  • Scaffold


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