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Related Concept Videos

Renewal of Skin Epidermal Stem Cells01:12

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The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
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Related Experiment Video

Updated: Sep 13, 2025

Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis
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Optimizing standardized lab-grown skin substitutes evidences a proliferation-differentiation switch based on ascorbic

Angie Katherine Molina-Oviedo1, Ilaria Sorrentino1, Irene Clares-Pedrero2

  • 1Department of Neurosciences and Biomedical Sciences, University Carlos III of Madrid, 28903 Madrid, Spain.

Iscience
|July 30, 2025
PubMed
Summary
This summary is machine-generated.

Ascorbic acid (AA) levels regulate skin cell development. Low AA promotes progenitor-like cells and better skin structure, while high AA induces motility and poor stratification in bioengineered skin models.

Keywords:
BiochemistryBiological sciencesCell biology

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Area of Science:

  • Biotechnology
  • Dermatology
  • Cell Biology

Background:

  • Developing bioengineered human skin requires understanding dermal-epidermal interactions.
  • Metabolites from the dermis can influence epidermal development and cell phenotype.

Purpose of the Study:

  • To investigate the role of ascorbic acid (AA) as a dermis-donated metabolite in modulating keratinocyte phenotype and epidermal development.
  • To determine the optimal concentration of AA for achieving desired cellular phenotypes in bioengineered skin constructs.

Main Methods:

  • Utilized immortalized keratinocytes and organotypic skin cultures.
  • Administered L-ascorbic acid 2-phosphate (A2P), a stable AA derivative, at varying concentrations.
  • Assessed cellular phenotypes, including clonogenicity, nuclear/cytoplasmic ratio, progenitor marker expression, and epithelial stratification.

Main Results:

  • A specific concentration (2 μg/mL A2P) induced a basal-like keratinocyte phenotype with increased progenitor markers and clonogenicity.
  • Higher A2P concentrations led to intracellular AA accumulation, promoting a motile cell status.
  • In organotypic cultures, 2 μg/mL A2P improved epithelial layering, while higher doses impaired stratification.

Conclusions:

  • Ascorbic acid levels critically influence keratinocyte commitment to differentiation versus self-renewal.
  • Controlled AA levels are essential for achieving functional epidermal architecture in bioengineered skin.
  • Findings provide insights into optimizing regenerative outcomes for skin tissue engineering.