Epidermal keratinocyte self-renewal is dependent upon dermal integrity

Area of Science:

• Dermatology
• Stem Cell Biology
• Tissue Engineering

Background:

• The epidermis constantly renews itself through cell division.
• Stem cells are likely present in the epidermis for self-renewal.
• The role of the dermis in epidermal self-renewal is not fully understood.

Purpose of the Study:

• To investigate the role of the dermis in maintaining epidermal self-renewal.
• To determine if epidermal self-renewal depends on a heterologous cell type, similar to the hematopoietic system.

Main Methods:

• Development of a mouse model for studying epidermal self-renewal.
• Grafting of separated epidermis onto mouse fascia or granulation tissue.
• Assessment of keratinocyte clonogenic capacity and self-renewal in vitro.
• Analysis of epidermal graft appearance and histology over time.

Main Results:

• Grafted epidermis reconstituted stratified squamous epithelium but showed reduced keratinocyte clonogenic capacity and self-renewal in vitro.
• Epidermal grafts initially hyperplastic, became atrophic after 40-70 days.
• The presence of dermis in grafts partially alleviated the failure of keratinocyte self-renewal.

Conclusions:

• The dermis plays a functional role in maintaining epidermal stem cell function.
• Loss of dermal support leads to impaired keratinocyte self-renewal in epidermal grafts.
• Findings have implications for clinical applications of cultured keratinocytes in wound healing.