Telomerase mRNA Enhances Human Skin Engraftment for Wound Healing

Deep skin wounds represent a serious condition and frequently require split‐thickness skin grafts (STSG) to heal. The application of autologous human‐skin‐cell‐suspension (hSCS) requires less donor skin than STSG without compromising the healing capacity. Impaired function and replicative ability of...

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Bibliographic Details
Published in:Advanced healthcare materials Vol. 13; no. 2; pp. e2302029 - n/a
Main Authors: Chang, David F., Court, Karem A., Holgate, Rhonda, Davis, Elizabeth A., Bush, Katie A., Quick, Andrew P., Spiegel, Aldona J., Rahimi, Maham, Cooke, John P., Godin, Biana
Format: Journal Article
Language:English
Published: Germany Wiley Subscription Services, Inc 01.01.2024
Subjects:
Animals
Autografts
Cellular Senescence - genetics
Damage
DNA damage
Gene expression
Humans
Keratinocytes
lipid nanoparticles
Lipids
Mice
mRNA
Nanoparticles
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA-directed DNA polymerase
Senescence
Skin
skin equivalence
Skin grafts
Telomerase
Telomerase - genetics
Telomerase reverse transcriptase
Telomeres
Thickness
Transfection
Wound Healing
lipid nanoparticles
wound healing
mRNA
skin equivalence
telomerase
ISSN:2192-2640, 2192-2659, 2192-2659
Online Access:Get full text
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Summary:Deep skin wounds represent a serious condition and frequently require split‐thickness skin grafts (STSG) to heal. The application of autologous human‐skin‐cell‐suspension (hSCS) requires less donor skin than STSG without compromising the healing capacity. Impaired function and replicative ability of senescent cutaneous cells in the aging skin affects healing with autologous hSCS. Major determinants of senescence are telomere erosion and DNA damage. Human telomerase reverse transcriptase (hTERT) adds telomeric repeats to the DNA and can protect against DNA damage. Herein, hTERT mRNA lipid nanoparticles (LNP) are proposed and evaluated for enhancing cellular engraftment and proliferation of hSCS. Transfection with optimized hTERT mRNA LNP system enables delivery and expression of mRNA in vitro in keratinocytes, fibroblasts, and in hSCS prepared from donors’ skin. Telomerase activity in hSCS is significantly increased. hTERT mRNA LNP enhance the generation of a partial‐thickness human skin equivalent in the mouse model, increasing hSCS engraftment (Lamin) and proliferation (Ki67), while reducing cellular senescence (p21) and DNA damage (53BP1). Human telomerase reverse transcriptase mRNA lipid nanoparticles (hTERT mRNA LNP) are formulated for improved healing of deep skin wounds using human skin cells suspension (hSCS). Transfection with optimized hTERT mRNA LNP enables delivery and expression of mRNA in hSCS in vitro. hTERT mRNA LNP‐treated hSCS enhances skin regeneration in partial‐thickness human‐skin equivalent in mice, increasing hSCS engraftment/proliferation, while reducing senescence/DNA‐damage.
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Rhonda Holgate: Investigation, Methodology, Writing – original draft/ review & editing
Andrew Quick: Conceptualization, Data curation
Katie Bush: Conceptualization, Data curation, Methodology, Writing – review & editing
Aldona J. Spiegel: Methodology, Resources
John Cooke: Conceptualization, Data curation, Funding acquisition, Project administration, Resources, Supervision, Writing – review & editing
Senior authors
Maham Rahimi: Methodology, Resources
Authors contributed equally to the manuscript
David Chang: Investigation, Methodology, Writing – original draft/ review & editing
Biana Godin: Conceptualization, Data curation, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing
Elizabeth Davis: Data curation, Project administration
Author Contributions
Karem Court: Investigation, Methodology, Writing – original draft/ review & editing
ISSN:2192-2640
2192-2659
2192-2659
DOI:10.1002/adhm.202302029