Recellularized human dermis for testing gene electrotransfer ex vivo

Area of Science:

• Biotechnology
• Tissue Engineering
• Gene Therapy

Background:

• Gene electrotransfer (GET) is a versatile in vivo gene delivery method.
• Preclinical skin studies face challenges due to differences in electrical conductivity between animal and human dermis.
• Developing accurate human skin models is crucial for optimizing gene delivery.

Purpose of the Study:

• To develop an ex vivo model using recellularized human dermis for gene electrotransfer.
• To create a more accurate preclinical model for human skin gene delivery studies.

Main Methods:

• Decellularized human dermis (DermACELL®) was cultured with fibroblasts and keratinocytes for 4 weeks.
• Recellularized constructs underwent air-liquid interface culture to promote epithelial stratification.
• Gene delivery parameters were tested using firefly luciferase expression after GET.

Main Results:

• Recellularized dermis exhibited fibroblast infiltration and stratified epithelial layers resembling native human skin.
• Gene electrotransfer resulted in sustained luciferase expression for up to one week.
• The model demonstrated structural and functional similarity to native human skin.

Conclusions:

• Recellularized human dermis provides an effective 3D ex vivo model for preclinical gene delivery studies.
• This model overcomes limitations of animal models for skin gene electrotransfer research.
• The developed model aids in optimizing gene delivery parameters for human skin applications.