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Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.

Publication ,  Journal Article
Eoh, JH; Shen, N; Burke, JA; Hinderer, S; Xia, Z; Schenke-Layland, K; Gerecht, S
Published in: Acta biomaterialia
April 2017

Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in over proliferation and graft failure. In this study, human induced-pluripotent stem cells (hiPSCs) were differentiated into early smooth muscle cells, seeded onto a hybrid poly(ethylene glycol) dimethacrylate/poly (l-lactide) (PEGdma-PLA) scaffold and cultured in a bioreactor while exposed to pulsatile flow, towards maturation into contractile smooth muscle tissue. We evaluated the effects of pulsatile flow on cellular organization as well as elastin expression and assembly in the engineered tissue compared to a static control through immunohistochemistry, gene expression and functionality assays. We show that culturing under pulsatile flow resulted in organized and functional hiPSC derived smooth muscle tissue. Immunohistochemistry analysis revealed hiPSC-smooth muscle tissue with robust, well-organized cells and elastic fibers and the supporting microfibril proteins necessary for elastic fiber assembly. Through qRT-PCR analysis, we found significantly increased expression of elastin, fibronectin, and collagen I, indicating the synthesis of necessary extracellular matrix components. Functionality assays revealed that hiPSC-smooth muscle tissue cultured in the bioreactor had an increased calcium signaling and contraction in response to a cholinergic agonist, significantly higher mature elastin content and improved mechanical properties in comparison to the static control. The findings presented here detail an effective approach to engineering elastic human vascular smooth muscle tissue with the functionality necessary for tissue engineering and regenerative medicine applications.Obtaining robust, mature elastic fibers is a key obstacle in tissue-engineered blood vessels. Human induced-pluripotent stem cells have become of interest due to their ability to supplement tissue engineered scaffolds. Their ability to differentiate into cells of vascular lineages with defined phenotypes serves as a potential solution to a major cause of graft failure in which phenotypic shifts in smooth muscle cells lead to over proliferation and occlusion of the graft. Herein, we have differentiated human induced-pluripotent stem cells in a pulsatile flow bioreactor, resulting in vascular smooth muscle tissue with robust elastic fibers and enhanced functionality. This study highlights an effective approach to engineering elastic functional vascular smooth muscle tissue for tissue engineering and regenerative medicine applications.

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Published In

Acta biomaterialia

DOI

EISSN

1878-7568

ISSN

1742-7061

Publication Date

April 2017

Volume

52

Start / End Page

49 / 59

Related Subject Headings

  • Up-Regulation
  • Tissue Scaffolds
  • Tissue Engineering
  • Muscle, Smooth, Vascular
  • Microfluidics
  • Induced Pluripotent Stem Cells
  • Humans
  • Extracellular Matrix Proteins
  • Equipment Design
  • Elastin
 

Citation

APA
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Eoh, J. H., Shen, N., Burke, J. A., Hinderer, S., Xia, Z., Schenke-Layland, K., & Gerecht, S. (2017). Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells. Acta Biomaterialia, 52, 49–59. https://doi.org/10.1016/j.actbio.2017.01.083
Eoh, Joon H., Nian Shen, Jacqueline A. Burke, Svenja Hinderer, Zhiyong Xia, Katja Schenke-Layland, and Sharon Gerecht. “Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.Acta Biomaterialia 52 (April 2017): 49–59. https://doi.org/10.1016/j.actbio.2017.01.083.
Eoh JH, Shen N, Burke JA, Hinderer S, Xia Z, Schenke-Layland K, et al. Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells. Acta biomaterialia. 2017 Apr;52:49–59.
Eoh, Joon H., et al. “Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.Acta Biomaterialia, vol. 52, Apr. 2017, pp. 49–59. Epmc, doi:10.1016/j.actbio.2017.01.083.
Eoh JH, Shen N, Burke JA, Hinderer S, Xia Z, Schenke-Layland K, Gerecht S. Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells. Acta biomaterialia. 2017 Apr;52:49–59.
Journal cover image

Published In

Acta biomaterialia

DOI

EISSN

1878-7568

ISSN

1742-7061

Publication Date

April 2017

Volume

52

Start / End Page

49 / 59

Related Subject Headings

  • Up-Regulation
  • Tissue Scaffolds
  • Tissue Engineering
  • Muscle, Smooth, Vascular
  • Microfluidics
  • Induced Pluripotent Stem Cells
  • Humans
  • Extracellular Matrix Proteins
  • Equipment Design
  • Elastin