Construction of three-dimensional vascularized cardiac tissue with cell sheet engineering

Katsuhisa Sakaguchi, Tatsuya Shimizu, Teruo Okano

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Construction of three-dimensional (3D) tissues with pre-isolated cells is a promising achievement for novel medicine and drug-discovery research. Our laboratory constructs 3D tissues with an innovative and unique method for layering multiple cell sheets. Cell sheets maintain a high-efficiently regenerating function, because of the higher cell density and higher transplantation efficiency, compared to other cell-delivery methods. Cell sheets have already been applied in clinical applications for regenerative medicine in treating patients with various diseases. Therefore, in our search to develop a more efficient treatment with cell sheets, we are constructing 3D tissues by layering cell sheets. Native animal tissues and organs have an abundance of capillaries to supply oxygen and nutrients, and to remove waste molecules. In our investigation of vascularized cardiac cell sheets, we have found that endothelial cells within cell sheets spontaneously form blood vessel networks as in vivo capillaries. To construct even thicker 3D tissues by layering multiple cell sheets, it is critical to have a medium or blood flow within the vascular networks of the cell sheets. Therefore, to perfuse medium or blood in the cell sheet vascular network to maintain the viability of all cells, we developed two types of vascular beds; (1) a femoral muscle-based vascular bed, and (2) a synthetic collagen gel-based vascular bed. Both vascular beds successfully provide the critical flow of culture medium, which allows 12-layer cell sheets to survive. Such bioreactor systems, when combined with cell sheet engineering techniques, have produced functional vascularized 3D tissues. Here we explain and discuss the various processes to obtain vascular networks by properly connecting cell sheets and the engineering of 3D tissues.

Original languageEnglish
Pages (from-to)83-88
Number of pages6
JournalJournal of Controlled Release
Volume205
DOIs
Publication statusPublished - 2015 Jan 6

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Cell Engineering
Blood Vessels
Animal Structures
Regenerative Medicine
Bioreactors
Drug Discovery
Thigh
Culture Media
Blood Cells
Cell Survival

Keywords

  • Bioreactor
  • Cell sheet
  • Tissue engineering
  • Vascularization

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Construction of three-dimensional vascularized cardiac tissue with cell sheet engineering. / Sakaguchi, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo.

In: Journal of Controlled Release, Vol. 205, 06.01.2015, p. 83-88.

Research output: Contribution to journalArticle

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