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Corneal Tissue Engineering: An In Vitro Model of the Stromal-nerve Interactions of the Human Cornea
Published on: January 24, 2018
Tissue engineering of skin and cornea: Development of new models for in vitro studies
Claudie Paquet1, Danielle Larouche, Francis Bisson
1Laboratoire d'Organogénèse Expérimentale, Centre de Recherche FRSQ du CHA Universitaire de Québec, and Département de Chirurgie et d'Oto-rhino-laryngologie et Ophtalmologie, Université Laval, Québec, Canada.
Abstract:
Human beings are greatly preoccupied with the unavoidable nature of aging. While the biological processes of senescence and aging are the subjects of intense investigations, the molecular mechanisms linking aging with disease and death are yet to be elucidated. Tissue engineering offers new models to study the various processes associated with aging. Using keratin 19 as a stem cell marker, our studies have revealed that stem cells are preserved in human skin reconstructed by tissue engineering and that the number of epithelial stem cells varies according to the donor's age. As with skin, human corneas can also be engineered in vitro. Among the epithelial cells used for reconstructing skin and corneas, significant age-dependent variations in the expression of the transcription factor Sp1 were observed. Culturing skin epithelial cells with a feeder layer extended their life span in culture, likely by preventing Sp1 degradation in epithelial cells, therefore demonstrating the pivotal role played by this transcription factor in cell proliferation. Finally, using the human tissue-engineered skin as a model, we linked Hsp27 activation with skin differentiation.
Insights
Tissue engineering preserves stem cells in human skin and corneas, revealing age-dependent changes in Sp1 expression linked to cell proliferation and differentiation.
Area of Science:
- Biogerontology
- Tissue Engineering
- Molecular Biology
Background:
- Aging is a complex process with poorly understood molecular mechanisms linking senescence to disease and mortality.
- Tissue engineering provides innovative models for studying age-related biological changes.
- Stem cells play a crucial role in tissue maintenance and regeneration, but their behavior during aging requires further investigation.
Purpose of the Study:
- To investigate the presence and age-dependency of stem cells in engineered human skin and corneas.
- To explore the role of the transcription factor Sp1 in age-related changes within epithelial cells.
- To elucidate the molecular mechanisms underlying cell proliferation and differentiation in engineered tissues.
Main Methods:
- Utilized keratin 19 as a stem cell marker in tissue-engineered human skin.
- Engineered human corneas in vitro using epithelial cells.
- Analyzed age-dependent variations in Sp1 expression in epithelial cells from engineered skin and corneas.
- Investigated the effect of feeder layer co-culture on epithelial cell lifespan and Sp1 degradation.
- Examined the relationship between Hsp27 activation and skin differentiation in engineered skin models.
Main Results:
- Stem cells were successfully preserved in tissue-engineered human skin, with numbers varying by donor age.
- Significant age-dependent variations in Sp1 expression were observed in epithelial cells used for skin and cornea engineering.
- Co-culturing skin epithelial cells with a feeder layer extended their lifespan, likely by inhibiting Sp1 degradation.
- This suggests a critical role for Sp1 in regulating epithelial cell proliferation.
- Hsp27 activation was linked to skin differentiation in the engineered skin model.
Conclusions:
- Tissue engineering is a valuable tool for studying aging processes in human skin and corneas.
- The transcription factor Sp1 is a key regulator of cell proliferation and its expression is age-dependent.
- Feeder layer culture can mitigate Sp1 degradation, extending cell lifespan.
- Hsp27 activation is associated with the differentiation of engineered skin.

