Optimizing standardized lab-grown skin substitutes evidences a proliferation-differentiation switch based on ascorbic acid Articles uri icon

authors

  • MOLINA OVIEDO, ANGIE KATHERINE
  • SORRENTINO, ILARIA
  • CLARES PEDRERO, IRENE
  • SALAMANCA GONZALEZ, CELINA
  • AREVALO NUÑEZ DE ARENAS, EDUARDO
  • MAZARIEGOS, MARINA S.
  • CABAÑAS, CARLOS
  • MEDRAÑO FERNANDEZ, IRIA

publication date

  • August 2025

start page

  • 1

end page

  • 27

issue

  • 8, 113066

volume

  • 28

International Standard Serial Number (ISSN)

  • 2589-0042

abstract

  • Developing standardized bioengineered constructs that accurately replicate human skin is a largely sought-after goal. Pathways initiated at the nurturing interface with the dermal compartment have the potential to modulate the developing epidermal architecture. Here, we identified ascorbic acid, a dermis-donated metabolite, as key in modulating the phenotypical identity of immortalized keratinocytes. Priming monolayers with 2 ...g/mL of the culture-stable derivative L-ascorbic acid 2-phosphate (A2P) led to the emergence of a basal-like phenotype within the cells, which showed increased clonogenicity, nuclear/cytoplasmic ratio, and upregulation of progenitor markers. Instead, surpassing this dose induced intracellular ascorbic acid accumulation and promoted a motile status. In organotypic cultures, pre-incubation of founding keratinocytes with 2 ...g/mL of A2P improved epithelial layering, whereas higher pretreatments resulted in poor stratification. These findings suggest that ascorbic acid levels in the self-renewing epithelium have a fundamental role in determining whether cells initially commit to differentiation, ultimately influencing regenerative outcomes.

subjects

  • Biology and Biomedicine