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一种使用划痕全层人类皮肤移植构建肥厚性瘢痕的新型裸鼠模型。

A Novel Nude Mouse Model of Hypertrophic Scarring Using Scratched Full Thickness Human Skin Grafts.

作者信息

Alrobaiea Saad M, Ding Jie, Ma Zengshuan, Tredget Edward E

机构信息

Wound Healing Research Group, Department of Surgery, University of Alberta , Edmonton, Canada .

Wound Healing Research Group, Department of Surgery, University of Alberta, Edmonton, Canada.; Divisions of Plastic and Reconstructive Surgery and Critical Care, University of Alberta, Edmonton, Canada.

出版信息

Adv Wound Care (New Rochelle). 2016 Jul 1;5(7):299-313. doi: 10.1089/wound.2015.0670.

DOI:10.1089/wound.2015.0670
PMID:27366591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4900225/
Abstract

Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder that develops following deep skin injury. HTS can cause deformities, functional disabilities, and aesthetic disfigurements. The pathophysiology of HTS is not understood due to, in part, the lack of an ideal animal model. We hypothesize that human skin with deep dermal wounds grafted onto athymic nude mice will develop a scar similar to HTS. Our aim is to develop a representative animal model of human HTS. Thirty-six nude mice were grafted with full thickness human skin with deep dermal scratch wound before or 2 weeks after grafting or without scratch. The scratch on the human skin grafts was made using a specially designed jig that creates a wound >0.6 mm in depth. The xenografts were morphologically analyzed by digital photography. Mice were euthanized at 1, 2, and 3 months postoperatively for histology and immunohistochemistry analysis. The mice developed raised and firm scars in the scratched xenografts with more contraction, increased infiltration of macrophage, and myofibroblasts compared to the xenografts without deep dermal scratch wound. Scar thickness and collagen bundle orientation and morphology resembled HTS. The fibrotic scars in the wounded human skin were morphologically and histologically similar to HTS, and human skin epithelial cells persisted in the remodeling tissues for 1 year postengraftment. Deep dermal injury in human skin retains its profibrotic nature after transplantation, affording a novel model for the assessment of therapies for the treatment of human fibroproliferative disorders of the skin.

摘要

增生性瘢痕(HTS)是一种在深度皮肤损伤后发生的真皮层纤维增生性疾病。HTS可导致畸形、功能障碍和美观缺陷。部分由于缺乏理想的动物模型,HTS的病理生理学尚未明确。我们假设将带有深度真皮伤口的人皮肤移植到无胸腺裸鼠身上会形成类似于HTS的瘢痕。我们的目的是建立一种具有代表性的人HTS动物模型。36只裸鼠在移植前、移植后2周或不进行划痕的情况下,被移植了带有深度真皮划痕伤口的全层人皮肤。人皮肤移植物上的划痕是使用专门设计的夹具制作的,该夹具可造成深度大于0.6毫米的伤口。通过数码摄影对异种移植物进行形态学分析。术后1、2和3个月对小鼠实施安乐死以进行组织学和免疫组织化学分析。与没有深度真皮划痕伤口的异种移植物相比,有划痕的异种移植物中的小鼠形成了凸起且坚硬的瘢痕,收缩更多,巨噬细胞和成肌纤维细胞浸润增加。瘢痕厚度、胶原束方向和形态与HTS相似。受伤人皮肤中的纤维化瘢痕在形态学和组织学上与HTS相似,并且人皮肤上皮细胞在移植后1年内持续存在于重塑组织中。人皮肤的深度真皮损伤在移植后保留其促纤维化特性,为评估治疗人类皮肤纤维增生性疾病的疗法提供了一种新模型。

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本文引用的文献

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The therapeutic potential of a C-X-C chemokine receptor type 4 (CXCR-4) antagonist on hypertrophic scarring in vivo.C-X-C趋化因子受体4(CXCR-4)拮抗剂对体内增生性瘢痕的治疗潜力。
Wound Repair Regen. 2014 Sep-Oct;22(5):622-30. doi: 10.1111/wrr.12208.
2
Fibroblasts in fibrosis: novel roles and mediators.纤维化中的成纤维细胞:新作用与介质
Front Pharmacol. 2014 May 27;5:123. doi: 10.3389/fphar.2014.00123. eCollection 2014.
3
Regenerative healing, scar-free healing and scar formation across the species: current concepts and future perspectives.跨物种的再生愈合、无瘢痕愈合和瘢痕形成:当前概念与未来展望
Exp Dermatol. 2014 Sep;23(9):615-9. doi: 10.1111/exd.12457. Epub 2014 Jul 21.
4
The Importance of Mast Cells in Dermal Scarring.肥大细胞在皮肤瘢痕形成中的重要性。
Adv Wound Care (New Rochelle). 2014 Apr 1;3(4):356-365. doi: 10.1089/wound.2013.0457.
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A novel murine model of hypertrophic scarring using subcutaneous infusion of bleomycin.一种使用皮下注射博来霉素的增生性瘢痕的新型鼠模型。
Plast Reconstr Surg. 2014 Jan;133(1):69-78. doi: 10.1097/01.prs.0000436821.26709.a7.
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Biomed Res Int. 2013;2013:423147. doi: 10.1155/2013/423147. Epub 2013 Sep 3.
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Mast cell activity in the healing wound: more than meets the eye?在愈合伤口中的肥大细胞活性:比所见更多?
Exp Dermatol. 2013 Aug;22(8):507-10. doi: 10.1111/exd.12169. Epub 2013 Jun 27.
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Wound repair and regeneration.伤口修复与再生。
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