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Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function.

Publication ,  Journal Article
Liau, B; Christoforou, N; Leong, KW; Bursac, N
Published in: Biomaterials
December 2011

Recent advances in pluripotent stem cell research have provided investigators with potent sources of cardiogenic cells. However, tissue engineering methodologies to assemble cardiac progenitors into aligned, 3-dimensional (3D) myocardial tissues capable of physiologically relevant electrical conduction and force generation are lacking. In this study, we introduced 3D cell alignment cues in a fibrin-based hydrogel matrix to engineer highly functional cardiac tissues from genetically purified mouse embryonic stem cell-derived cardiomyocytes (CMs) and cardiovascular progenitors (CVPs). Procedures for CM and CVP derivation, purification, and functional differentiation in monolayer cultures were first optimized to yield robust intercellular coupling and maximize velocity of action potential propagation. A versatile soft-lithography technique was then applied to reproducibly fabricate engineered cardiac tissues with controllable size and 3D architecture. While purified CMs assembled into a functional 3D syncytium only when supplemented with supporting non-myocytes, purified CVPs differentiated into cardiomyocytes, smooth muscle, and endothelial cells, and autonomously supported the formation of functional cardiac tissues. After a total culture time similar to period of mouse embryonic development (21 days), the engineered cardiac tissues exhibited unprecedented levels of 3D organization and functional differentiation characteristic of native neonatal myocardium, including: 1) dense, uniformly aligned, highly differentiated and electromechanically coupled cardiomyocytes, 2) rapid action potential conduction with velocities between 22 and 25 cm/s, and 3) significant contractile forces of up to 2 mN. These results represent an important advancement in stem cell-based cardiac tissue engineering and provide the foundation for exploiting the exciting progress in pluripotent stem cell research in the future tissue engineering therapies for heart disease.

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Published In

Biomaterials

DOI

EISSN

1878-5905

ISSN

0142-9612

Publication Date

December 2011

Volume

32

Issue

35

Start / End Page

9180 / 9187

Related Subject Headings

  • Tissue Scaffolds
  • Tissue Engineering
  • Rats
  • Pluripotent Stem Cells
  • Myocytes, Cardiac
  • Myocardium
  • Mice
  • Fibroblasts
  • Electrophysiological Phenomena
  • Coculture Techniques
 

Citation

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Liau, B., Christoforou, N., Leong, K. W., & Bursac, N. (2011). Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function. Biomaterials, 32(35), 9180–9187. https://doi.org/10.1016/j.biomaterials.2011.08.050
Liau, Brian, Nicolas Christoforou, Kam W. Leong, and Nenad Bursac. “Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function.Biomaterials 32, no. 35 (December 2011): 9180–87. https://doi.org/10.1016/j.biomaterials.2011.08.050.
Liau B, Christoforou N, Leong KW, Bursac N. Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function. Biomaterials. 2011 Dec;32(35):9180–7.
Liau, Brian, et al. “Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function.Biomaterials, vol. 32, no. 35, Dec. 2011, pp. 9180–87. Epmc, doi:10.1016/j.biomaterials.2011.08.050.
Liau B, Christoforou N, Leong KW, Bursac N. Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function. Biomaterials. 2011 Dec;32(35):9180–9187.
Journal cover image

Published In

Biomaterials

DOI

EISSN

1878-5905

ISSN

0142-9612

Publication Date

December 2011

Volume

32

Issue

35

Start / End Page

9180 / 9187

Related Subject Headings

  • Tissue Scaffolds
  • Tissue Engineering
  • Rats
  • Pluripotent Stem Cells
  • Myocytes, Cardiac
  • Myocardium
  • Mice
  • Fibroblasts
  • Electrophysiological Phenomena
  • Coculture Techniques