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微流控皮肤芯片与脉管系统,用于重现皮肤组织的免疫反应。

Microfluidic skin chip with vasculature for recapitulating the immune response of the skin tissue.

机构信息

Department of Chemical Engineering, Hongik University, Republic of Korea.

Department of Dermatology, Seoul National University Hospital, Republic of Korea.

出版信息

Biotechnol Bioeng. 2020 Jun;117(6):1853-1863. doi: 10.1002/bit.27320. Epub 2020 Mar 4.

Abstract

There is a considerable need for cell-based in vitro skin models for studying dermatological diseases and testing cosmetic products, but current in vitro skin models lack physiological relevance compared to human skin tissue. For example, many dermatological disorders involve complex immune responses, but current skin models are not capable of recapitulating the phenomena. Previously, we reported development of a microfluidic skin chip with a vessel structure and vascular endothelial cells. In this study, we cocultured dermal fibroblasts and keratinocytes with vascular endothelial cells, human umbilical vascular endothelial cells. We verified the formation of a vascular endothelium in the presence of the dermis and epidermis layers by examining the expression of tissue-specific markers. As the vascular endothelium plays a critical role in the migration of leukocytes to inflammation sites, we incorporated leukocytes in the circulating media and attempted to mimic the migration of neutrophils in response to external stimuli. Increased secretion of cytokines and migration of neutrophils was observed when the skin chip was exposed to ultraviolet irradiation, showing that the microfluidic skin chip may be useful for studying the immune response of the human tissue.

摘要

对于研究皮肤病和测试化妆品的细胞体外皮肤模型有很大的需求,但与人体皮肤组织相比,目前的体外皮肤模型缺乏生理相关性。例如,许多皮肤病涉及复杂的免疫反应,但目前的皮肤模型无法重现这些现象。以前,我们报道了一种具有血管结构和血管内皮细胞的微流控皮肤芯片的开发。在这项研究中,我们将真皮成纤维细胞和角质形成细胞与血管内皮细胞(人脐静脉内皮细胞)共培养。通过检查组织特异性标记物的表达,我们验证了在真皮和表皮层存在的情况下血管内皮的形成。由于血管内皮在白细胞向炎症部位迁移中起着关键作用,我们将白细胞纳入循环介质中,并试图模拟中性粒细胞对外界刺激的迁移。当皮肤芯片暴露于紫外线照射时,观察到细胞因子的分泌增加和中性粒细胞的迁移,表明微流控皮肤芯片可能有助于研究人体组织的免疫反应。

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