Key Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, First Hospital Affiliated to General Hospital of PLA, 51 Fu Cheng Road, Beijing, 100048, People's Republic of China.
School of Medicine, Nankai University, Tianjin, 300052, People's Republic of China.
Stem Cell Res Ther. 2018 Jul 4;9(1):179. doi: 10.1186/s13287-018-0929-7.
Damaged or malfunctioning sweat glands (SGs) after a burn injury would cause significant hyperthermia and even death, and there is an unmet need for effective treatment. Genetically reprogrammed stem cells show their potential advantages for inducing SG repair and regeneration.
The expression of interferon regulatory factor 6 (IRF6) in skin was tested by immunofluorescence, and Irf6 was overexpressed in epidermal progenitors (EPs) to stimulate SG differentiation. For in-vivo studies, second- and third-degree mouse burn wounds were treated with subcutaneous injection of EPs and Irf6-transfected cells, and cell retention and therapeutic effects were assessed.
IRF6 demonstrated differential expression between the footpad and dorsal skin and was upregulated along with embryonic and postnatal SG development. The Irf6-transfected cells converted their cell phenotypes as seen by gene and protein expression analyses and their morphology closely resembled epidermal-derived glandular cells. Inductive SG cell (SGC) transplantation and in-vivo tracing examination demonstrated that they could survive at damaged sites for 14 days. In comparison, the positive effects of inductive SGCs only result in restoring SG function in second-degree burn wounds but not in third-degree burn wounds as assessed by both perspiration tests and morphological analyses.
These results suggest that IRF6 plays an important role in directing glandular lineage differentiation of Eps, but that the therapeutic efficacy of inductive SGCs may be restricted to the burn environment.
烧伤后受损或功能失调的汗腺会导致明显的体温过高，甚至死亡，因此需要有效的治疗方法。基因重编程的干细胞在诱导汗腺修复和再生方面显示出其潜在的优势。
通过免疫荧光检测干扰素调节因子 6（IRF6）在皮肤中的表达，并在表皮祖细胞（EPs）中过表达 Irf6 以刺激 SG 分化。对于体内研究，用 EP 和 Irf6 转染细胞的皮下注射治疗二级和三级小鼠烧伤创面，并评估细胞保留和治疗效果。
IRF6 在足垫和背部皮肤之间表现出差异表达，并随着胚胎和出生后 SG 的发育而上调。转染 Irf6 的细胞通过基因和蛋白表达分析转化其细胞表型，其形态与表皮衍生的腺细胞非常相似。诱导性 SGC 移植和体内示踪检查表明，它们可以在受损部位存活 14 天。相比之下，诱导性 SGC 的积极作用仅能恢复二级烧伤创面的 SG 功能，而不能恢复三级烧伤创面的功能，这可以通过出汗测试和形态学分析来评估。
这些结果表明，IRF6 在指导 Eps 的腺体谱系分化中起重要作用，但诱导性 SGC 的治疗效果可能仅限于烧伤环境。
