Establishing a Xenograft Model with CD-1 Nude Mice to Study Human Skin Wound Repair
Copyright © 2023 by the American Society of Plastic Surgeons..
BACKGROUND: A significant gap exists in the translatability of small-animal models to human subjects. One important factor is poor laboratory models involving human tissue. Thus, the authors have created a viable postnatal human skin xenograft model using athymic mice.
METHODS: Discarded human foreskins were collected following circumcision. All subcutaneous tissue was removed from these samples sterilely. Host CD-1 nude mice were then anesthetized, and dorsal skin was sterilized. A 1.2-cm-diameter, full-thickness section of dorsal skin was excised. The foreskin sample was then placed into the full-thickness defect in the host mice and sutured into place. Xenografts underwent dermal wounding using a 4-mm punch biopsy after engraftment. Xenografts were monitored for 14 days after wounding and then harvested.
RESULTS: At 14 days postoperatively, all mice survived the procedure. Grossly, the xenograft wounds showed formation of a human scar at postoperative day 14. Hematoxylin and eosin and Masson trichome staining confirmed scar formation in the wounded human skin. Using a novel artificial intelligence algorithm using picrosirius red staining, scar formation was confirmed in human wounded skin compared with the unwounded skin. Histologically, CD31 + immunostaining confirmed vascularization of the xenograft. The xenograft exclusively showed human collagen type I, CD26 + , and human nuclear antigen in the human scar without any staining of these human markers in the murine skin.
CONCLUSION: The proposed model demonstrates wound healing to be a local response from tissue resident human fibroblasts and allows for reproducible evaluation of human skin wound repair in a preclinical model.
CLINICAL RELEVANCE STATEMENT: Radiation-induced fibrosis is a widely prevalent clinical phenomenon without a well-defined treatment at this time. This study will help establish a small-animal model to better understand and develop novel therapeutics to treat irradiated human skin.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:153 |
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| Enthalten in: |
Plastic and reconstructive surgery - 153(2024), 1 vom: 01. Jan., Seite 121-128 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abbas, Darren B [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 19.01.2024 Date Revised 08.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1097/PRS.0000000000010465 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Abbas, Darren B |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Establishing a Xenograft Model with CD-1 Nude Mice to Study Human Skin Wound Repair |
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| 500 | |a Date Revised 08.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 by the American Society of Plastic Surgeons. | ||
| 520 | |a BACKGROUND: A significant gap exists in the translatability of small-animal models to human subjects. One important factor is poor laboratory models involving human tissue. Thus, the authors have created a viable postnatal human skin xenograft model using athymic mice | ||
| 520 | |a METHODS: Discarded human foreskins were collected following circumcision. All subcutaneous tissue was removed from these samples sterilely. Host CD-1 nude mice were then anesthetized, and dorsal skin was sterilized. A 1.2-cm-diameter, full-thickness section of dorsal skin was excised. The foreskin sample was then placed into the full-thickness defect in the host mice and sutured into place. Xenografts underwent dermal wounding using a 4-mm punch biopsy after engraftment. Xenografts were monitored for 14 days after wounding and then harvested | ||
| 520 | |a RESULTS: At 14 days postoperatively, all mice survived the procedure. Grossly, the xenograft wounds showed formation of a human scar at postoperative day 14. Hematoxylin and eosin and Masson trichome staining confirmed scar formation in the wounded human skin. Using a novel artificial intelligence algorithm using picrosirius red staining, scar formation was confirmed in human wounded skin compared with the unwounded skin. Histologically, CD31 + immunostaining confirmed vascularization of the xenograft. The xenograft exclusively showed human collagen type I, CD26 + , and human nuclear antigen in the human scar without any staining of these human markers in the murine skin | ||
| 520 | |a CONCLUSION: The proposed model demonstrates wound healing to be a local response from tissue resident human fibroblasts and allows for reproducible evaluation of human skin wound repair in a preclinical model | ||
| 520 | |a CLINICAL RELEVANCE STATEMENT: Radiation-induced fibrosis is a widely prevalent clinical phenomenon without a well-defined treatment at this time. This study will help establish a small-animal model to better understand and develop novel therapeutics to treat irradiated human skin | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 700 | 1 | |a Griffin, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Fahy, Evan J |e verfasserin |4 aut | |
| 700 | 1 | |a Spielman, Amanda F |e verfasserin |4 aut | |
| 700 | 1 | |a Guardino, Nicholas J |e verfasserin |4 aut | |
| 700 | 1 | |a Pu, Adrian |e verfasserin |4 aut | |
| 700 | 1 | |a Lintel, Hendrik |e verfasserin |4 aut | |
| 700 | 1 | |a Lorenz, H Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Longaker, Michael T |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Derrick C |e verfasserin |4 aut | |
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