AI Article Synopsis
- The study developed two types of artificial human tissue substitutes: bilayered full-thickness stromal-epithelial substitutes (SESS) and epithelial substitutes (ESS), to investigate the maturation of the extracellular matrix in a controlled setting.
- Results showed that SESS epithelium demonstrated higher differentiation and extracellular matrix production compared to ESS, which had more proliferative cells but less matrix development.
- The findings highlight the importance of epithelial-stromal interactions in tissue engineering and suggest that both SESS and ESS can be effective models for studying metabolic pathways and tissue development.
Article Abstract
Background: Tissue engineering techniques offer new strategies to understand complex processes in a controlled and reproducible system. In this study, we generated bilayered human tissue substitutes consisting of a cellular connective tissue with a suprajacent epithelium (full-thickness stromal-epithelial substitutes or SESS) and human tissue substitutes with an epithelial layer generated on top of an acellular biomaterial (epithelial substitutes or ESS). Both types of artificial tissues were studied at sequential time periods to analyze the maturation process of the extracellular matrix.
Results: Regarding epithelial layer, ESS cells showed active proliferation, positive expression of cytokeratin 5, and low expression of differentiation markers, whereas SESS epithelium showed higher differentiation levels, with a progressive positive expression of cytokeratin 10 and claudin. Stromal cells in SESS tended to accumulate and actively synthetize extracellular matrix components such as collagens and proteoglycans in the stromal area in direct contact with the epithelium (zone 1), whereas these components were very scarce in ESS. Regarding the basement membrane, ESS showed a partially differentiated structure containing fibronectin-1 and perlecan. However, SESS showed higher basement membrane differentiation, with positive expression of fibronectin 1, perlecan, nidogen 1, chondroitin-6-sulfate proteoglycans, agrin, and collagens types IV and VII, although this structure was negative for lumican. Finally, both ESS and SESS proved to be useful tools for studying metabolic pathway regulation, revealing differential activation and upregulation of the transforming growth factor-β pathway in ESS and SESS.
Conclusions: These results confirm the relevance of epithelial-stromal interaction for extracellular matrix development and differentiation, especially regarding basement membrane components, and suggest the usefulness of bilayered artificial tissue substitutes to reproduce ex vivo the extracellular matrix maturation and development process of human tissues.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575135 | PMC |
| http://dx.doi.org/10.1186/s12915-024-02065-y | DOI Listing |
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