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.

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.

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