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人羊膜上皮细胞来源的外泌体经皮给药可改善小鼠银屑病样皮肤损伤。

Topical administration of the secretome derived from human amniotic epithelial cells ameliorates psoriasis-like skin lesions in mice.

机构信息

State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

Department of Dermatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

出版信息

Stem Cell Res Ther. 2022 Aug 3;13(1):393. doi: 10.1186/s13287-022-03091-9.

Abstract

BACKGROUND

Psoriasis is a chronic inflammatory skin disease. Tissue stem cells have exhibited a therapeutic effect on psoriatic mice. However, the therapeutic effect of topical administration of the secretome derived from tissue stem cells on psoriasis has not been reported.

METHODS

The secretome from human amniotic epithelial cells (AEC-SC) and human umbilical cord mesenchymal stem cells (UMSC-SC) was topically administrated on the back of imiquimod-induced psoriasis-like mice. Subsequently, we observed the skin lesions and skin inflammation of psoriasis-like mice. Next, we further analyzed the paracrine factors in AEC-SC and UMSC-SC by protein chips. Lastly, the effect of the crucial paracrine factor was investigated by imiquimod-induced psoriasis-like mice.

RESULTS

We found that AEC-SC had a better therapeutic effect on attenuating psoriasis-like skin lesions including skin scales, skin redness and skin thickness than UMSC-SC, and it had a better regulatory effect on keratinocyte hyperproliferation and altered differentiation. Thus, we focused on AEC-SC. Further study showed that AEC-SC reduced the infiltration of neutrophils and interleukin-17-producing T cells. Next, the analysis of AEC-SC with protein chip revealed that the levels of anti-inflammatory factor interleukin-1 receptor antagonist (IL-1ra) were much higher in AEC-SC compared to that in UMSC-SC. More importantly, the beneficial effect of AEC-SC on psoriasis-like skin lesions and skin inflammation of mice were significantly impaired when neutralizing with IL-1ra antibody, while the recombinant human IL-1ra showed a less protective effect than AEC-SC.

CONCLUSIONS

The present study demonstrated that AEC-SC could efficiently ameliorate psoriasis-like skin lesions and skin inflammation and IL-1ra plays an essential role. Therefore, topical administration of AEC-SC may provide a novel strategy for treating psoriasis-like inflammatory skin diseases.

摘要

背景

银屑病是一种慢性炎症性皮肤病。组织干细胞已在银屑病小鼠模型中显示出治疗效果。然而,尚未有关于组织干细胞来源的外泌体经皮给药治疗银屑病的报道。

方法

将人羊膜上皮细胞(AEC-SC)和人脐带间充质干细胞(UMSC-SC)的外泌体局部涂抹于咪喹莫特诱导的银屑病样小鼠背部,观察银屑病样小鼠的皮肤病变和皮肤炎症。然后,我们通过蛋白质芯片进一步分析 AEC-SC 和 UMSC-SC 的旁分泌因子。最后,通过咪喹莫特诱导的银屑病样小鼠研究关键旁分泌因子的作用。

结果

我们发现 AEC-SC 对减轻银屑病样皮肤病变(包括皮肤鳞屑、皮肤发红和皮肤增厚)的疗效优于 UMSC-SC,对角质形成细胞过度增殖和分化改变具有更好的调节作用。因此,我们专注于 AEC-SC。进一步的研究表明,AEC-SC 减少了中性粒细胞和白介素-17 产生的 T 细胞的浸润。接下来,通过蛋白质芯片分析 AEC-SC 发现,与 UMSC-SC 相比,AEC-SC 中的抗炎因子白细胞介素-1 受体拮抗剂(IL-1ra)水平要高得多。更重要的是,当用 IL-1ra 抗体中和时,AEC-SC 对小鼠银屑病样皮肤病变和皮肤炎症的有益作用显著受损,而重组人 IL-1ra 的保护作用不及 AEC-SC。

结论

本研究表明 AEC-SC 可有效改善银屑病样皮肤病变和皮肤炎症,IL-1ra 发挥重要作用。因此,AEC-SC 的经皮给药可能为治疗银屑病样炎症性皮肤病提供一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9238/9351215/6ae153410c16/13287_2022_3091_Fig1_HTML.jpg

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