Human adipose stem cells cell sheet constructs impact epidermal morphogenesis in full-thickness excisional wounds

Area of Science:

• Regenerative Medicine
• Tissue Engineering
• Dermatology

Background:

• Skin wound healing is a complex process.
• Tissue engineering offers a promising strategy for skin regeneration.
• Stem cells, particularly human adipose-derived stem cells (hASCs), are key players in regenerative medicine.

Purpose of the Study:

• To investigate the potential of hASCs cell sheets (CS) for full-thickness skin wound regeneration.
• To evaluate the impact of thermoresponsive versus standard cell culture surfaces on CS stability and regenerative outcomes.
• To explore the mechanisms by which hASCs CS influence skin repair, including vascularization and epidermal morphogenesis.

Main Methods:

• Human adipose-derived stem cells (hASCs) were cultured to form cell sheets (CS) using thermoresponsive and standard surfaces.
• Three-layered hASCs CS constructs were created and transplanted into full-thickness excisional mouse skin wounds.
• Skin regeneration, including epidermal thickness, maturation, vascularization, and hair follicle formation, was assessed.

Main Results:

• hASCs CS constructs, particularly those from thermoresponsive surfaces, demonstrated enhanced stability and promoted prolonged cell engraftment.
• Transplanted hASCs influenced neotissue vascularization and significantly promoted epidermal morphogenesis, leading to thicker, more mature epidermis with rete ridges.
• Constructs from thermoresponsive surfaces resulted in a higher number of hair follicles, indicating improved skin regeneration.

Conclusions:

• hASCs CS-based constructs are effective for treating full-thickness skin wounds.
• The fabrication conditions, specifically the use of thermoresponsive surfaces, significantly impact the stability of CS constructs and enhance skin regeneration outcomes.
• hASCs CS promote skin repair primarily through paracrine signaling, influencing vascularization and epidermal development, rather than through cell transdifferentiation.