Supp Dorothy M
Research Department, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio.
Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Adv Wound Care (New Rochelle). 2019 Feb 1;8(2):77-89. doi: 10.1089/wound.2018.0828. Epub 2019 Feb 13.
Keloid scarring is a disfiguring fibroproliferative disorder that can significantly impair the quality of life in affected individuals. The mechanisms that initiate keloid scarring are incompletely understood, and keloids remain one of the most challenging skin conditions to treat. Keloids are unique to humans; thus, the lack of adequate animal models has hindered research efforts aimed at prevention and effective therapeutic intervention. In the absence of a suitable animal model, keloid researchers often rely on studying excised keloid scar tissue and keloid-derived cultured cells. Recently, models have been described that involve transplantation to mice of reconstructed skin containing keloid-derived fibroblasts and/or keratinocytes. These mouse-human hybrid animal models display some similarities with keloids and may enable investigation of novel therapies, although no model yet recapitulates all the features of human keloid scarring. Differences in skin physiology and modes of healing contribute to challenges in modeling keloids in laboratory animals. Furthermore, recent studies suggest that cells of the immune system contribute to keloid pathology. The need to use immunodeficient hosts for transplanted human keloid cells in recently described animal models precludes studying the role of the immune system in keloid scarring. Future animal models may take advantage of humanized mice with immune systems reconstituted using human immune cells. Such models, when combined with grafted tissues prepared using keloid-derived cells, might enable investigation of complex interactions between systemic and local factors that combine to promote keloid scar formation and may aid in the development of novel therapies.
瘢痕疙瘩是一种毁容性的纤维增生性疾病,会严重损害患者的生活质量。引发瘢痕疙瘩的机制尚未完全明确,瘢痕疙瘩仍是最难治疗的皮肤疾病之一。瘢痕疙瘩是人类特有的;因此,缺乏合适的动物模型阻碍了旨在预防和有效治疗干预的研究工作。在没有合适动物模型的情况下,瘢痕疙瘩研究人员通常依靠研究切除的瘢痕疙瘩组织和瘢痕疙瘩来源的培养细胞。最近,已经描述了一些模型,这些模型涉及将含有瘢痕疙瘩来源的成纤维细胞和/或角质形成细胞的重建皮肤移植到小鼠体内。这些小鼠 - 人类杂交动物模型与瘢痕疙瘩有一些相似之处,可能有助于研究新的治疗方法,尽管目前还没有一个模型能完全重现人类瘢痕疙瘩的所有特征。皮肤生理学和愈合方式的差异给在实验动物中建立瘢痕疙瘩模型带来了挑战。此外,最近的研究表明免疫系统细胞参与了瘢痕疙瘩的病理过程。在最近描述的动物模型中,需要使用免疫缺陷宿主来移植人类瘢痕疙瘩细胞,这就排除了研究免疫系统在瘢痕疙瘩形成中的作用。未来的动物模型可能会利用用人免疫细胞重建免疫系统的人源化小鼠。当这种模型与使用瘢痕疙瘩来源的细胞制备的移植组织相结合时,可能有助于研究全身和局部因素之间的复杂相互作用,这些因素共同促进瘢痕疙瘩的形成,并可能有助于开发新的治疗方法。