Mechanical stimuli enhance simultaneous differentiation into oesophageal cell lineages in a double‐layered tubular scaffold

• Published in: Journal of tissue engineering and regenerative medicine Vol. 13; no. 8; pp. 1394 - 1405
• Main Authors: Wu, Yanru, Kang, Yun Gyeong, Kim, In Gul, Kim, Ji Eun, Lee, Eun Jin, Chung, Eun‐Jae, Shin, Jung‐Woog
• Format: Journal Article
• Language: English
• Published: England Hindawi Limited 01.08.2019
• Subjects: Biomechanics; Bioreactors; Cell culture; Cell differentiation; Construction; Differentiation; Electrospinning; electrospun scaffold; epithelial differentiation; Esophagus; Fibers; hollow organ bioreactor; Hydrostatic pressure; Incubation; Mechanical stimuli; Mechanical tests; Mesenchymal stem cells; Mesenchyme; muscle differentiation; Muscles; oesophageal tissue engineering; Reagents; Regenerative medicine; Scaffolds; Shear flow; Shear stress; Stem cells; Stimuli; Tissue engineering; electrospun scaffold; epithelial differentiation; muscle differentiation; oesophageal tissue engineering; mesenchymal stem cells; hollow organ bioreactor
• ISSN: 1932-6254; 1932-7005
• DOI: 10.1002/term.2881

The tissue‐engineered oesophagus serves as an alternative and promising therapeutic approach for long‐gap oesophageal replacement. This study proposes an advanced in vitro culture platform focused on construction of the oesophagus by combining an electrospun double‐layered tubular scaffold, stem cells, biochemical reagents, and biomechanical factors. Human mesenchymal stem cells were seeded onto the inner and outer surfaces of the scaffold. Mechanical stimuli were applied with a hollow organ bioreactor along with different biochemical reagents inside and outside of the scaffold. Electrospun fibres in a tubular scaffold were found to be randomly and circumferentially oriented for the inner and outer surfaces, respectively. Amongst the two types of mechanical stimuli, the intermittent shear flow that can simultaneously cause circumferential stretching due to hydrostatic pressure, and shear stress caused by flow on the inner surface, was found to be more effective for simultaneous differentiation into epithelial and muscle lineage than steady shear flow. Under these conditions, the expression of epithelial markers on the inner surface was significantly observed, although it was minimal on the outer surface. Muscle differentiation showed the opposite expression pattern. Meanwhile, the mechanical tests showed that the strength of the scaffold was improved after incubation for 14 days. We have developed a potential platform for tissue‐engineered oesophagus construction. Specifically, simultaneous differentiation into epithelial and muscle lineages can be achieved by utilizing the double‐layered scaffold and appropriate mechanical stimulation.