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Engineering human skin model innervated with itch sensory neuron-like cells differentiated from induced pluripotent stem cells
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2021-08-10 , DOI: 10.1002/btm2.10247
Zongyou Guo 1 , Chi-Kun Tong 1 , Joanna Jacków 1 , Yanne S Doucet 1 , Hasan E Abaci 1 , Wangyong Zeng 1 , Corey Hansen 1 , Ryota Hayashi 1 , Dominick DeLorenzo 1 , Avina Rami 1 , Alberto Pappalardo 1 , Ellen A Lumpkin 1 , Angela M Christiano 1
Affiliation  

Atopic dermatitis (AD), driven by interleukins (IL-4/IL-13), is a chronic inflammatory skin disease characterized by intensive pruritus. However, it is unclear how immune signaling and sensory response pathways cross talk with each other. We differentiated itch sensory neuron-like cells (ISNLCs) from iPSC lines. These ISNLCs displayed neural markers and action potentials and responded specifically to itch-specific stimuli. These ISNLCs expressed receptors specific for IL-4/IL-13 and were activated directly by the two cytokines. We successfully innervated these ISNLCs into full thickness human skin constructs. These innervated skin grafts can be used in clinical applications such as wound healing. Moreover, the availability of such innervated skin models will be valuable to develop drugs to treat skin diseases such as AD.

中文翻译:


由诱导多能干细胞分化而来的瘙痒感觉神经元样细胞支配的工程人体皮肤模型



特应性皮炎 (AD) 由白细胞介素 (IL-4/IL-13) 驱动,是一种以剧烈瘙痒为特征的慢性炎症性皮肤病。然而,目前尚不清楚免疫信号传导和感觉反应途径如何相互作用。我们从 iPSC 系中分化出瘙痒感觉神经元样细胞 (ISNLC)。这些 ISNLC 显示神经标记和动作电位,并对瘙痒特异性刺激做出特异性反应。这些 ISNLC 表达 IL-4/IL-13 特异性受体,并直接被这两种细胞因子激活。我们成功地将这些 ISNLC 神经支配到全层人类皮肤结构中。这些受神经支配的皮肤移植物可用于伤口愈合等临床应用。此外,这种受神经支配的皮肤模型的可用性对于开发治疗 AD 等皮肤病的药物将很有价值。
更新日期:2021-08-10
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