Keloid-derived, plasma/fibrin-based skin equivalents generate de novo dermal and epidermal pathology of keloid fibrosis in a mouse model.

Keloids are wounding-induced tumor-like human scars. Unclear etiology and lack of animal models to reveal disease mechanisms and invent therapies deepen the grievous health and psychosocial state of vulnerable individuals. Epitomizing the injury-repair environment which triggers and fosters keloid f...

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Publicado en:Wound Repair & Regeneration Vol. 24; no. 2; pp. 302 - 317
Autores principales: Lee, Yun ‐ Shain, Hsu, Tim, Chiu, Wei ‐ Chih, Sarkozy, Heidi, Kulber, David A., Choi, Aaron, Kim, Elliot W., Benya, Paul D., Tuan, Tai ‐ Lan
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell Mar/Apr2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar/Apr2016
      vid: 24
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1111/wrr.12397
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        atl: Keloid-derived, plasma/fibrin-based skin equivalents generate de novo dermal and epidermal pathology of keloid fibrosis in a mouse model.
      aug:
        au:
          Lee, Yun ‐ Shain
          Hsu, Tim
          Chiu, Wei ‐ Chih
          Sarkozy, Heidi
          Kulber, David A.
          Choi, Aaron
          Kim, Elliot W.
          Benya, Paul D.
          Tuan, Tai ‐ Lan
        affil: The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles California
      sug:
        subj:
          Keloid Pathology
          Skin Pathology
          Keloid Etiology
          Animal Studies
          Mice
          Models, Biological
          In Vivo Studies
          Keratinocytes
          Fibroblasts
          Xenografts
          T-Tests
          Data Analysis Software
          Wound Healing
      ab: Keloids are wounding-induced tumor-like human scars. Unclear etiology and lack of animal models to reveal disease mechanisms and invent therapies deepen the grievous health and psychosocial state of vulnerable individuals. Epitomizing the injury-repair environment which triggers and fosters keloid formation and essential dermal/epidermal interactions in disease development, the novel animal model was established by implanting porous polyethylene ring-supported plasma/fibrin-based epidermal-dermal skin constructs on the dorsum of athymic NU/J mice. The implants were stable to 18 weeks, contained abundant human cells, and remodeled to yield scar architecture characteristic of keloid fibrosis compared with normal implants and clinical specimens: (1) macroscopic convex or nodular scar morphology; (2) morphogenesis and accumulation of large collagen bundles from collagen-null initial constructs; (3) epidermal hyperplasia, aberrant epidermal-dermal patency, and features of EMT; (4) increased vasculature, macrophage influx, and aggregation; and (5) temporal-spatial increased collagen-inducing PAI-1 and its interactive partner uPAR expression. Development of such pathology in the NU/J host suggests that T-cell participation is less important at this stage than at keloid initiation. These accessible implants also healed secondary excisional wounds, enabling clinically relevant contemporaneous wounding and treatment strategies, and evaluation. The model provides a robust platform for studying keloid formation and testing knowledge-based therapies.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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