自组装神经支配血管芯片用于伤害感受研究。
Self-assembled innervated vasculature-on-a-chip to study nociception.
机构信息
Department of Biomedical Engineering, Duke University, Durham, NC, United States of America.
Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, United States of America.
出版信息
Biofabrication. 2023 Apr 13;15(3). doi: 10.1088/1758-5090/acc904.
Nociceptor sensory neurons play a key role in eliciting pain. An active crosstalk between nociceptor neurons and the vascular system at the molecular and cellular level is required to sense and respond to noxious stimuli. Besides nociception, interaction between nociceptor neurons and vasculature also contributes to neurogenesis and angiogenesis.models of innervated vasculature can greatly help delineate these roles while facilitating disease modeling and drug screening. Herein, we report the development of a microfluidic-assisted tissue model of nociception in the presence of microvasculature. The self-assembled innervated microvasculature was engineered using endothelial cells and primary dorsal root ganglion (DRG) neurons. The sensory neurons and the endothelial cells displayed distinct morphologies in presence of each other. The neurons exhibited an elevated response to capsaicin in the presence of vasculature. Concomitantly, increased transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor expression was observed in the DRG neurons in presence of vascularization. Finally, we demonstrated the applicability of this platform for modeling nociception associated with tissue acidosis. While not demonstrated here, this platform could also serve as a tool to study pain resulting from vascular disorders while also paving the way towards the development of innervated microphysiological models.
伤害感受器感觉神经元在引发疼痛中起关键作用。需要在分子和细胞水平上在伤害感受器神经元和血管系统之间进行积极的串扰,以感知和响应有害刺激。除了伤害感受之外,伤害感受器神经元和脉管系统之间的相互作用还有助于神经发生和血管生成。有神经支配的脉管系统模型可以极大地帮助阐明这些作用,同时促进疾病建模和药物筛选。在此,我们报告了在微脉管系统存在下伤害感受的微流控辅助组织模型的开发。使用内皮细胞和原代背根神经节 (DRG) 神经元来工程化自组装的有神经支配的微血管。在彼此存在的情况下,神经元和内皮细胞表现出不同的形态。在脉管系统存在的情况下,神经元对辣椒素表现出更高的反应。同时,在血管生成的情况下,DRG 神经元中瞬时受体电位阳离子通道亚家族 V 成员 1 (TRPV1) 受体的表达增加。最后,我们证明了该平台在模拟与组织酸中毒相关的伤害感受方面的适用性。虽然这里没有证明,但该平台还可以作为研究血管疾病引起的疼痛的工具,同时为有神经支配的微生理模型的开发铺平道路。
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