Esophagus tissue engineering: in vitro generation of esophageal epithelial cell sheets and viability on scaffold

Saxena, Amulya K.; Ainoedhofer, Herwig; Höllwarth, Michael E.

doi:10.1016/j.jpedsurg.2009.01.019

Cited by 45 publications

(36 citation statements)

References 26 publications

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“…Proliferative basal cells with cytoplasmic staining for CK14 and nuclear staining for PCNA are identified in the correct location 28 in both TEE (Fig. 2G, H) and native esophagus (Fig.…”

Section: Resultsmentioning

confidence: 90%

“…The pursuit of viable clinical esophageal replacements that do not rely on native tissue substitutions has led to investigations in numerous animal models, including rat, [5][6][7]28,[30][31][32] dog, 3,33-37 pig, [38][39][40] rabbit, 41 and sheep. 2 In some experiments in which a defect was patched, it is unclear if the esophagus was actually engineered or if tissue ingrowth from healthy surrounding tissue bridged the defect.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

Spurrier

Speer

Hou

et al. 2015

Tissue Engineering Part A

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Purpose: Tissue-engineered esophagus (TEE) may serve as a therapeutic replacement for absent foregut. Most prior esophagus studies have favored microdesigned biomaterials and yielded epithelial growth alone. None have generated human TEE with mesenchymal components. We hypothesized that sufficient progenitor cells might only require basic support for successful generation of murine and human TEE. Materials and Methods: Esophageal organoid units (EOUs) were isolated from murine or human esophagi and implanted on a polyglycolic acid/poly-l-lactic acid collagen-coated scaffold in adult allogeneic or immunedeficient mice. Alternatively, EOU were cultured for 10 days in vitro prior to implantation. Results: TEE recapitulated all key components of native esophagus with an epithelium and subjacent muscularis. Differentiated suprabasal and proliferative basal layers of esophageal epithelium, muscle, and nerve were identified. Lineage tracing demonstrated that multiple EOU could contribute to the epithelium and mesenchyme of a single TEE. Cultured murine EOU grew as an expanding sphere of proliferative basal cells on a neuromuscular network that demonstrated spontaneous peristalsis in culture. Subsequently, cultured EOU generated TEE. Conclusions: TEE forms after transplantation of mouse and human organ-specific stem/progenitor cells in vivo on a relatively simple biodegradable scaffold. This is a first step toward future human therapies.

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“…Proliferative basal cells with cytoplasmic staining for CK14 and nuclear staining for PCNA are identified in the correct location 28 in both TEE (Fig. 2G, H) and native esophagus (Fig.…”

Section: Resultsmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

Spurrier

Speer

Hou

et al. 2015

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…Such assays have been performed in studies with a similar remit where the necessity of validating tissuespecific cell behavior and functionality in vitro before moving toward in vivo, were specifically highlighted. [25,27] After 3 d of mOEC culture on top of buffered peptide hydrogels, the preferential peptide hydrogels were identified as PGD-AlphaProC and PGD-CGD2 as demonstrated by the typical cobblestone-like morphology and tight junction formation between cells (ZO-1 expression), resulting in an epithelial sheet-like formation. Positive expression of cytokeratins was also observed.…”

Section: Discussionmentioning

confidence: 99%

“…The ability to deliver the hydrogel endosocopically is feasible due to the shear-thinning and self-assembling properties of these www.afm-journal.de www.advancedsciencenews.com hydrogels. [24] Once the hydrogel is delivered to the injury site, it can be anticipated that host fibroblasts and epithelial cells from adjacent healthy tissue would migrate into the hydrogel, permit re-epithelialization [25] and production of matrix, and permit normal function, which is to act as a protective, semipermeable barrier. [26,27] Rapid restitution of the mucosal barrier would result in a reduced inflammatory response resulting in subsequent modulation of fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Peptide Hydrogels—A Tissue Engineering Strategy for the Prevention of Oesophageal Strictures

Kumar

Workman

O’Brien

et al. 2017

Adv Funct Materials

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Endoscopic treatment of Barrett's oesophagus often leads to further damage of healthy tissue causing fibrotic tissue formation termed as strictures. This study shows that synthetic, self-assembling peptide hydrogels (PeptiGelDesign) support the activity and function of primary oesophageal cells, leading to epithelialization and stratification during in vitro 3D co-culture. Following buffering in culture media, rat oesophageal stromal fibroblasts (rOSFs) are incorporated into a library of peptide hydrogels, whereas mouse oesophageal epithelial cells (mOECs) are seeded on the surface. Optimal hydrogels (PGD-AlphaProC and PGD-CGD2) support mOEC viability (>95%), typical cell morphology (cobblestone-like), and slower migration over a shorter distance compared to a collagen control, at 48 h. Positive expression of typical epithelial markers (ZO-1 and cytokeratins) is detected using immunocytochemistry at day 3 in culture. Furthermore, optimal hydrogels are identified which support rOSF viability (>95%) with homogeneous distribution when incorporated into the hydrogels and also promote the secretion of collagen type I detected using an enzyme linked immunosorbent assay (ELISA), at day 7. A 3D co-culture model using optimal hydrogels for both cell types supports a stratified epithelial layer (expressing involucrin and AE1/AE3 markers). Findings from this study could lead to the use of peptide hydrogels as a minimally invasive endoscopic therapy to manage oesophageal strictures.

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“…Esophagus is a muscular tube that transverses three anatomical planes (neck, thorax, and abdomen) and serves as a conduit to transport food and fluids from mouth to the stomach [27]. To engineer long-term implants with no leak or stenosis and with epithelialization over the entire lumen of the implanted scaffold will be of paramount importance [28].…”

Section: Discussionmentioning

confidence: 99%

Tissue engineered esophagus by copper—small intestinal submucosa graft for esophageal repair in a canine model

Tan

Wang

Chen

et al. 2014

Sci. China Life Sci.

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Acellular porcine small intestinal submucosa (SIS) has been used for esophagoplasty with success in a canine model. However, it did not lead to complete epithelialization. For better reconstruction, a cellular component is required. Moreover, promotion of angiogenesis with copper has been widely recognized by basic research as well as clinical studies. In this study, we have evaluated the feasibility and effectiveness of combined Cu and SIS (SIS-Cu patch) for the esophageal repair using a canine model. Eighteen male beagle dogs were subjected to surgical resection to produce cervical esophageal defects (5 cm in length, 180° in range). SIS with Cu (5 or 25 μmol L 1 copper) or without Cu was patched on the esophageal defects. Barium esophagram and histology exam were carried out to evaluate the effectiveness of the therapy. As shown, the SIS-Cu graft promoted re-epithelialization, re-vascularization and muscular regeneration. SIS-Cu patch is more effective than SIS alone for esophageal repair, and the SIS+25 μmol L 1 Cu group demonstrated additional advantages over the SIS+5 μmol L 1

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Esophagus tissue engineering: in vitro generation of esophageal epithelial cell sheets and viability on scaffold

Cited by 45 publications

References 26 publications

Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

Peptide Hydrogels—A Tissue Engineering Strategy for the Prevention of Oesophageal Strictures

Tissue engineered esophagus by copper—small intestinal submucosa graft for esophageal repair in a canine model

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