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Cited by 38Xenotransplantation and immune responseDermatology and Skin DiseasesOrgan and Tissue Transplantation Research

Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells

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Agarwal, Yash, Beatty, Cole, Ho, Sara, Thurlow, Lance, Das, Antu, Kelly, Samantha, Castronova, Isabella, Salunke, Rajeev +4 more·2020·Scientific Reports
DOI 10.1038/s41598-020-71548-zPMC PMC7471691

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Abstract

The human skin is a significant barrier for protection against pathogen transmission. Rodent models used to investigate human-specific pathogens that target the skin are generated by introducing human skin grafts to immunocompromised rodent strains. Infection-induced immunopathogenesis has been separately studied in humanized rodent models developed with human lymphoid tissue and hematopoietic stem cell transplants. Successful co-engraftment of human skin, autologous lymphoid tissues, and autologous immune cells in a rodent model has not yet been achieved, though it could provide a means of studying the human immune response to infection in the human skin. Here, we introduce the human Skin and Immune System (hSIS)-humanized NOD- scid IL2Rγ null (NSG) mouse and Sprague–Dawley-Rag2 tm2hera Il2rγ tm1hera (SRG) rat models, co-engrafted with human full-thickness fetal skin, autologous fetal lymphoid tissues, and autologous fetal liver-derived hematopoietic stem cells. hSIS-humanized rodents demonstrate the development of human full-thickness skin, along with autologous lymphoid tissues, and autologous immune cells. These models also support human skin infection following intradermal inoculation with community-associated methicillin-resistant Staphylococcus aureus . The co-engraftment of these human skin and immune system components into a single humanized rodent model could provide a platform for studying human skin infections.

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Crossref · 10.1038/s41598-020-71548-z

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  • The mouse is a standard model for investigating skin development and disease in vivo.

    “The mouse is a standard model for investigating skin development and disease in vivo”

    From Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells (2022) · cites this paper as [14]

    The Introduction says in vivo models for studying skin-targeting insults and pathogens primarily involve mice and rats, and the Discussion calls rodent models primary platforms for investigating skin-associated diseases (page not provided). These passages support mice as a standard model for skin disease, but do not establish their standard use for investigating skin development. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The immune response and inflammatory processes involved in wound healing can vary between mice and humans.

    “Additionally, the immune response and inflammatory processes involved in wound healing can vary between mice and humans.”

    From Anti-Inflammatory and Histological Analysis of Skin Wound Healing through Topical Application of Mexican Propolis (2023) · cites this paper as [91]

    The Discussion says structural differences between human and rodent skin could lead to differences in cutaneous immune signaling and inflammatory responses. The Results describe wound healing in human skin grafts, but do not compare immune or inflammatory processes during wound healing in mice and humans. No page numbers are available in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Mice may exhibit a more robust or different immune response compared to humans, so the effects of propolis on immune modulation and inflammation observed in mice may not directly translate to humans.

    “Mice may exhibit a more robust or different immune response compared to humans, meaning that the effects of propolis on immune modulation and inflammation observed in mice may not directly translate to humans [91,92].”

    From Anti-Inflammatory and Histological Analysis of Skin Wound Healing through Topical Application of Mexican Propolis (2023) · cites this paper as [91]

    The Introduction and Discussion (page numbers not supplied) describe differences between human and rodent immune systems and warn that findings from traditional rodent models may not translate to humans. The paper does not address propolis or establish that mice have a more robust immune response, so those parts of the claim are unsupported. (LLM, conf=0.86)

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Cited by

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Authors
Agarwal, Y., Beatty, C., Ho, S., Thurlow, L., Das, A., Kelly, S., Castronova, I., Salunke, R., Biradar, S., Yeshi, T., Richardson, A., & Bility, M.
Affiliations
University of Pittsburgh (US)
Corresponding author
Bility, Moses
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-09-03
Volume
10
Issue
1
Pages
14598-14598
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-71548-z
PMC
PMC7471691
OpenAlex
W3082069952
Cited by
38
References
3
Citations by year
2026: 6 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 3 · 2021: 2
FWCI
2.96
Type
journal article
Language
en
Update notices
correction (2021-09-14)
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • University of Pittsburgh (P30 CA047904)
  • National Institutes of Health
  • National Cancer Institute (P30CA047904)
  • National Institute of Allergy and Infectious Diseases (R21AI135412)
  • Fogarty International Center (D43TW010039)
Topics
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Transplantation › Organ and Tissue Transplantation Research
Keywords
humanized mice, hematopoietic stem cells, skin infections, community-associated methicillin-resistant Staphylococcus aureus, immunopathogenesis
MeSH terms
Animals, Blood Cells, Disease Models, Animal, Humans, Lymphoid Tissue, Skin, Staphylococcal Infections, Transplantation, Autologous, Virus Replication, Skin Transplantation, Mice, SCID, Mice, Inbred NOD, Mice, Rats, Methicillin-Resistant Staphylococcus aureus

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