期刊
ADVANCED FUNCTIONAL MATERIALS
卷 27, 期 38, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201702424
关键词
Barrett's oesophagus; co-culture model; stiffness; synthetic peptide hydrogels
类别
资金
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council UK Regenerative Medicine Platform Hub [MR/K026682/1]
- EPSRC [EP/K016210/1]
- EPSRC [EP/K016210/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/K016210/1] Funding Source: researchfish
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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