Li Binghui, Xue Hang, Zhao Xiaobo, Weng Yuxiong, Li Gongchi, Wang Kun, Zhou Pan, Wu Youtong, Vankelecom Hugo, Chen Jianghai
1 Wuhan Liyuan Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China.
2 Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China.
Int J Low Extrem Wounds. 2019 Mar;18(1):42-55. doi: 10.1177/1534734618818909. Epub 2019 Jan 8.
Full-thickness skin wounds are common accidents. Although healing can be achieved by treatments like autologous skin grafts, donor site morbidity is hardly evitable. In this article, we provide compelling evidence demonstrating that artificial dermal template (ADT)-treated wound healing is achieved by regrowth of skin epidermis as well as adnexa without skin grafts by use of rodent models. First, by fixating a chamber to the wound edge, we confirmed that wound healing was achieved by regeneration instead of contracture. We found highly proliferative cells in adnexa in the newly formed skin. In the distal edge of newly formed skin, we identified immature hair follicles at early developing stages, suggesting they were newly regenerated. Second, we observed that the Lgr5-positive hair follicle stem cells contributed to formation of new hair follicles through a lineage tracing model. Also, Lgr6-positive cells were enriched in distal edge of newly developed skin. Finally, WNT signaling pathway mediators were highly expressed in the new skin epidermis and adnexa, implying a potential role of WNT signaling during ADT treatment-stimulated skin regrowth. Taken together, our findings demonstrated that full skin regrowth can be induced by ADT treatment alone, thus arguing for its wide clinical application in skin wound treatment.
全层皮肤伤口是常见的意外创伤。尽管通过自体皮肤移植等治疗方法可以实现伤口愈合,但供皮区的并发症几乎难以避免。在本文中,我们提供了令人信服的证据,证明在啮齿动物模型中,使用人工真皮模板(ADT)治疗的伤口愈合是通过皮肤表皮以及附属器的再生实现的,无需进行皮肤移植。首先,通过将一个腔室固定在伤口边缘,我们证实伤口愈合是通过再生而非挛缩实现的。我们在新形成皮肤的附属器中发现了高度增殖的细胞。在新形成皮肤的远端边缘,我们鉴定出处于早期发育阶段的未成熟毛囊,这表明它们是新再生的。其次,我们观察到Lgr5阳性毛囊干细胞通过谱系追踪模型促进了新毛囊的形成。此外,Lgr6阳性细胞在新发育皮肤的远端边缘富集。最后,WNT信号通路介质在新皮肤表皮和附属器中高度表达,这意味着WNT信号在ADT治疗刺激的皮肤再生过程中可能发挥作用。综上所述,我们的研究结果表明,仅通过ADT治疗就可以诱导全层皮肤再生,因此主张其在皮肤伤口治疗中的广泛临床应用。