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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| Veröffentlicht in: | Advanced healthcare materials 2024-01, Vol.13 (2), p.e2302029-n/a |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1002/adhm.202302029 |
| format | Article |
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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.</description><identifier>ISSN: 2192-2640</identifier><identifier>ISSN: 2192-2659</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.202302029</identifier><identifier>PMID: 37619534</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>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</subject><ispartof>Advanced healthcare materials, 2024-01, Vol.13 (2), p.e2302029-n/a</ispartof><rights>2023 Wiley‐VCH GmbH</rights><rights>2023 Wiley-VCH GmbH.</rights><rights>2024 Wiley‐VCH GmbH</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5499-bebd8b8ada25fcce0dcec864831bfbef1d9f9f2f87d7cdf7b791ec386d5b0e603</citedby><cites>FETCH-LOGICAL-c5499-bebd8b8ada25fcce0dcec864831bfbef1d9f9f2f87d7cdf7b791ec386d5b0e603</cites><orcidid>0000-0001-9457-1848 ; 0000-0003-2347-9205 ; 0000-0002-8040-320X ; 0000-0001-9798-8868 ; 0000-0002-8916-8461 ; 0000-0003-0033-9138 ; 0000-0002-6334-6960 ; 0000-0002-8725-3662 ; 0000-0002-0230-7490 ; 0000-0001-6089-6695</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.202302029$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.202302029$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,777,781,882,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37619534$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, David F.</creatorcontrib><creatorcontrib>Court, Karem A.</creatorcontrib><creatorcontrib>Holgate, Rhonda</creatorcontrib><creatorcontrib>Davis, Elizabeth A.</creatorcontrib><creatorcontrib>Bush, Katie A.</creatorcontrib><creatorcontrib>Quick, Andrew P.</creatorcontrib><creatorcontrib>Spiegel, Aldona J.</creatorcontrib><creatorcontrib>Rahimi, Maham</creatorcontrib><creatorcontrib>Cooke, John P.</creatorcontrib><creatorcontrib>Godin, Biana</creatorcontrib><title>Telomerase mRNA Enhances Human Skin Engraftment for Wound Healing</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>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.</description><subject>Animals</subject><subject>Autografts</subject><subject>Cellular Senescence - genetics</subject><subject>Damage</subject><subject>DNA damage</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Keratinocytes</subject><subject>lipid nanoparticles</subject><subject>Lipids</subject><subject>Mice</subject><subject>mRNA</subject><subject>Nanoparticles</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA-directed DNA polymerase</subject><subject>Senescence</subject><subject>Skin</subject><subject>skin equivalence</subject><subject>Skin grafts</subject><subject>Telomerase</subject><subject>Telomerase - genetics</subject><subject>Telomerase reverse transcriptase</subject><subject>Telomeres</subject><subject>Thickness</subject><subject>Transfection</subject><subject>Wound Healing</subject><issn>2192-2640</issn><issn>2192-2659</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtPxCAURonRqFG3Lk0TN25mBNpSWJmJrzHxkfiIS0LhMlNtQWGq8d-LGR0fG1nADZx7ws2H0DbBQ4Ix3Vdm2g0ppjlOm1hC65QIOqCsFMuLusBraCvGB5wWKwnjZBWt5RUjosyLdTS6hdZ3EFSErLu-HGXHbqqchpiN-0657OaxceluEpSddeBmmfUhu_e9M9kYVNu4ySZasaqNsPV5bqC7k-Pbw_Hg_Or07HB0PtBlIcSghtrwmiujaGm1Bmw0aM4KnpPa1mCJEVZYanllKm1sVVeCgM45M2WNgeF8Ax3MvU993UHqdrOgWvkUmk6FN-lVI3-_uGYqJ_5FEswLzARLhr1PQ_DPPcSZ7JqooW2VA99HSXlZJZSTKqG7f9AH3weX5pNUkKIqOeckUcM5pYOPMYBd_IZg-ZGQ_EhILhJKDTs_Z1jgX3kkQMyB16aFt390cnQ0vviWvwMZ0Z3p</recordid><startdate>20240101</startdate><enddate>20240101</enddate><creator>Chang, David F.</creator><creator>Court, Karem A.</creator><creator>Holgate, Rhonda</creator><creator>Davis, Elizabeth A.</creator><creator>Bush, Katie A.</creator><creator>Quick, Andrew P.</creator><creator>Spiegel, Aldona J.</creator><creator>Rahimi, Maham</creator><creator>Cooke, John P.</creator><creator>Godin, Biana</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QP</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T5</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7TO</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9457-1848</orcidid><orcidid>https://orcid.org/0000-0003-2347-9205</orcidid><orcidid>https://orcid.org/0000-0002-8040-320X</orcidid><orcidid>https://orcid.org/0000-0001-9798-8868</orcidid><orcidid>https://orcid.org/0000-0002-8916-8461</orcidid><orcidid>https://orcid.org/0000-0003-0033-9138</orcidid><orcidid>https://orcid.org/0000-0002-6334-6960</orcidid><orcidid>https://orcid.org/0000-0002-8725-3662</orcidid><orcidid>https://orcid.org/0000-0002-0230-7490</orcidid><orcidid>https://orcid.org/0000-0001-6089-6695</orcidid></search><sort><creationdate>20240101</creationdate><title>Telomerase mRNA Enhances Human Skin Engraftment for Wound Healing</title><author>Chang, David F. ; 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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.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37619534</pmid><doi>10.1002/adhm.202302029</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-9457-1848</orcidid><orcidid>https://orcid.org/0000-0003-2347-9205</orcidid><orcidid>https://orcid.org/0000-0002-8040-320X</orcidid><orcidid>https://orcid.org/0000-0001-9798-8868</orcidid><orcidid>https://orcid.org/0000-0002-8916-8461</orcidid><orcidid>https://orcid.org/0000-0003-0033-9138</orcidid><orcidid>https://orcid.org/0000-0002-6334-6960</orcidid><orcidid>https://orcid.org/0000-0002-8725-3662</orcidid><orcidid>https://orcid.org/0000-0002-0230-7490</orcidid><orcidid>https://orcid.org/0000-0001-6089-6695</orcidid></addata></record> |
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| 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 |
| title | Telomerase mRNA Enhances Human Skin Engraftment for Wound Healing |
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