Esophageal smooth muscle cells dedifferentiate with loss of α-smooth muscle actin expression after 8 weeks of explant expansion in vitro culture: Implications on esophagus tissue engineering

Kofler, Kristina; Ainoedhofer, Herwig; Tausendschön, J.; Höllwarth, Michael E.; Saxena, Amulya K.

doi:10.1007/s10353-011-0617-7

Cited by 6 publications

(2 citation statements)

References 38 publications

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“…Plasticity of smooth muscle and the switch between synthetic and contractile phenotype is an extensive area of study [7, 18, 19]. Different smooth muscle markers exist and their expression varies [18, 20]. At 2 weeks post-implantation, the engineered neuro-muscular tissue showed positive expression of α-smooth muscle actin.…”

Section: Discussionmentioning

confidence: 99%

Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold

Zakhem

Elbahrawy

Orlando

et al. 2015

Surgery

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Background There is an urgent need for gut lengthening secondary to massive resections of the gastrointestinal (GI) tract. In this study, we propose to evaluate the remodeling, vascularization and functionality of a chitosan-based tubular neuro-muscular tissue upon subcutaneous implantation in the back of athymic rats. Methods Aligned innervated smooth muscle sheets were bioengineered using human smooth muscle and neural progenitor cells. The innervated sheets were wrapped around tubular chitosan scaffolds. The engineered tubular neuro-muscular tissue was implanted subcutaneously in the back of athymic rats. The implant was harvested after 14 days and assessed for morphology, vascularization and functionality. Results Gross examination of the implants showed healthy color with no signs of inflammation. The implanted tissue became vascularized as demonstrated by gross and histological analysis. Chitosan supported the luminal patency of the tissue. The innervated muscle remodeled around the tubular chitosan scaffold. Smooth muscle maintained its circumferential alignment and contractile phenotype. Functionality of the implant was further characterized using real time force generation. Cholinergic response was demonstrated by robust contraction in response to Ach. VIP and EFS caused relaxation. In the presence of neurotoxin TTX, the magnitude of Ach-induced contraction and VIP-induced relaxation was attenuated while EFS-induced relaxation was completely abolished, indicating neuronal contribution to the response. Conclusion Our results indicated the successful subcutaneous implantation of engineered tubular neuro-muscular tissues. The tissues became vascularized and maintained their myogenic and neurogenic phenotype and function. This provides potential therapeutic prospects for providing implantable replacement GI segments for treating GI motility disorders.

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Section: Discussionmentioning

confidence: 99%

Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold

Zakhem

Elbahrawy

Orlando

et al. 2015

Surgery

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“…The explant technique is an established technique for the sourcing of SMC from vascular structures. 78 When compared with the enzymatic dissociation techniques, the explant technique requires additionally 10 days before sufficient cells are obtained to achieve reasonable numbers for expansion and 2 weeks until the culture plate wells are confluent. It could be presumed that because there is almost loss of α-SMA expression in almost half of the OESMC in 4 weeks, the enzymatic dissociation techniques could prove favorable in gaining this time of 4 weeks so that increased numbers of OESMC could retain their α-SMA expression that would be preferable in the hybrid construct approach.…”

Section: Smooth Muscle Cellsmentioning

confidence: 99%

Esophagus Tissue Engineering: Designing and Crafting the Components for the “Hybrid Construct” Approach

Saxena

2014

Eur J Pediatr Surg

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Although being a tubular structure, the esophagus is an extremely complex organ to engineer. To engineer an organ, its components and their structure and function must be well understood. With regards to esophagus, extensive investigations have been performed in experimental models to understand the nature of the esophageal epithelial cells with regards to their isolation, culture, and growth on scaffolds to generate epithelium. Special subpopulations of these cells have been identified that possess proliferative capabilities with subsequent differentiative capacity to generate epithelium. Studies have also been performed to obtain data on the possibilities of utilizing esophageal biopsies from esophagus damaged after caustic exposure for tissue engineering applications. Subsequently, attention is being paid to the esophageal smooth muscle which is an extremely complex structure responsible for the propulsive activities. In addition to the muscle complex, proper functioning of the esophagus will require understanding of the enteric nervous system (ENS) that controls the propulsive activity in a coordinated manner. Investigations have been performed to better understand the esophageal ENS and to isolate and maintain these cells under tissue culture conditions. Besides the cellular elements, studies have also been performed to seed these cells on scaffolds and study the constructs with regards to cell attachment and viability under tissue culture conditions. Tests have also been performed on native esophageal tissue to understand the functioning of this tissue under the effect of pharmacological agents and to establish norms to compare engineered esophageal tissue. Vascularization, which is a limiting factor in tissue engineering, has been approached with the in situ bioreactor concept using the omentum not only to provide vascular ingrowth but also to offer a pedicle for the engineered esophagus to enable its surgical transposition. This review offers an insight into the advances in esophagus tissue engineering in a large experimental model using the "hybrid construct" approach which advocates the precise engineering of the tubular gastrointestinal organs based on growth of specific cells on specially designed scaffolds and amalgamating them to create the desired complex tissue structure.

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Isolation, identification and culture of myenteric plexus cells from ovine esophagus

2013

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Esophageal smooth muscle cells dedifferentiate with loss of α-smooth muscle actin expression after 8 weeks of explant expansion in vitro culture: Implications on esophagus tissue engineering

Cited by 6 publications

References 38 publications

Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold

Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold

Esophagus Tissue Engineering: Designing and Crafting the Components for the “Hybrid Construct” Approach

Isolation, identification and culture of myenteric plexus cells from ovine esophagus

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