Telomerase mRNA Enhances Human Skin Engraftment for Wound Healing

Area of Science:

• Biotechnology
• Regenerative Medicine
• Dermatology

Background:

• Deep skin wounds often require split-thickness skin grafts (STSG), a procedure with limitations.
• Autologous human skin cell suspension (hSCS) offers an alternative but is hindered by cellular senescence in aging skin.
• Cellular senescence, driven by telomere erosion and DNA damage, impairs the healing capacity of hSCS.

Purpose of the Study:

• To evaluate the efficacy of human telomerase reverse transcriptase (hTERT) mRNA lipid nanoparticles (LNP) for enhancing hSCS.
• To investigate the potential of hTERT mRNA LNP to improve cellular engraftment and proliferation in hSCS.
• To assess the impact of hTERT mRNA LNP on reducing senescence and DNA damage in skin cells.

Main Methods:

• Developed and optimized an hTERT mRNA LNP system for efficient delivery and expression in skin cells.
• Transfected keratinocytes, fibroblasts, and hSCS with hTERT mRNA LNP in vitro.
• Evaluated the effect of hTERT mRNA LNP on a partial-thickness human skin equivalent in a mouse model.

Main Results:

• hTERT mRNA LNP successfully delivered and expressed mRNA in various skin cell types, significantly increasing telomerase activity in hSCS.
• In vivo studies demonstrated enhanced hSCS engraftment (Lamin marker) and proliferation (Ki67 marker).
• Treatment with hTERT mRNA LNP led to a reduction in cellular senescence (p21 marker) and DNA damage (53BP1 marker).

Conclusions:

• hTERT mRNA LNP represent a promising strategy for improving the regenerative potential of hSCS for wound healing.
• This approach effectively combats cellular senescence and DNA damage, key factors limiting the efficacy of hSCS in older individuals.
• The enhanced engraftment and proliferation observed suggest a significant advancement in skin regeneration therapies.