Human Tissue Procurement and Processing Core

人体组织采购和加工核心

• 批准号: 10594338
• 负责人: Kyle Eberlin
• 金额: $ 22.45万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594338
• 关键词: Animal Model; Autopsy; Biological Assay; Biological Markers; Biology; Brain; Cell Nucleus; Cells; Chronic; Collaborations; Collection; Data; Databases; Distal; Drug or chemical Tissue Distribution; Enrollment; Freezing; Ganglia; General Hospitals; Genetic; Genomics; Goals; Human; Individual; Informed Consent; Institutional Review Boards; Knowledge; Lead; Left; Massachusetts; Metadata; Molecular; Mus; Nerve; Neuraxis; Neuroma; Nociception; Nociceptors; Operative Surgical Procedures; Pain; Pain Clinics; Pain management; Pain quality; Patients; Peripheral; Phantom Limb; Phantom Limb Pain; Physiology; Positioning Attribute; Process; Protocols documentation; Publishing; Randomized; Reporter; Research Personnel; Resected; Resources; Running; Sampling; Secondary to; Source; Spinal Cord; Spinal Ganglia; Structure of trigeminal ganglion; Therapeutic; Tissue Banks; Tissue Procurements; Tissue Sample; Tissues; Translations; Work; chronic pain patient; chronic painful condition; clinical phenotype; clinical translation; design; effective therapy; experience; human tissue; improved; muscle reinnervation; novel; pain model; pain score; painful neuropathy; programs; sciatic nerve; therapeutic target; tissue processing; tool; tumor-immune system interactions

PROJECT SUMMARY (Human Tissue Procurement and Processing Core) Despite advances in our understanding of nociception in animal models, pain targets in mice have experienced decades of difficulty in translation to novel effective and safe treatments for patients with chronic pain. The lack of translation between mouse and human pain treatments has highlighted limitations of animal models of pain. Recent advances in applying single-cell genomics and physiology directly to human tissue positions our field to make important new advances in pain biology with improved opportunities for clinical translation. The Human Tissue Procurement and Processing Core will be responsible for obtaining high-quality tissue from post-mortem donors and chronic pain patients with informed consent. The experience of most forms of neuropathic pain begins with abnormal firing of peripheral nociceptors, whose cell bodies are in the dorsal root ganglia or trigeminal ganglia. These ganglia reside outside of the central nervous system and would make ideal pain therapeutic targets if they could be inhibited selectively. We thus propose to extract dorsal root ganglia, trigeminal ganglia and distal sciatic nerve from post-mortem human donors using an established rapid autopsy program at Massachusetts General Hospital. This IRB-approved protocol is already underway and has collected samples from > 25 donors, a selection of which were successfully processed for single-nucleus genomic assays. The Core will build upon these established tissue procurement and processing protocols in collaboration with other U19 Centers. To characterize molecular changes that occur in patients with chronic pain, patients with chronic phantom limb secondary to symptomatic neuromas will have their neuromas procured during muscle reinnervation surgery. This protocol is IRB approved and already enrolling. Fresh and frozen samples will be made available to Center investigators for single-cell genomic assays. The Core will also maintain a tissue bank of deidentified frozen tissues for distribution to Center investigators and investigators across the PRECISION Human Pain Network.

项目摘要（人体组织采购和加工核心） 尽管我们对动物模型的伤害感受的理解取得了进步，但小鼠的疼痛靶标仍经历了 为慢性疼痛患者转化为新颖有效治疗的新型有效治疗的困难数十年。缺乏 小鼠和人类疼痛治疗之间的翻译强调了动物疼痛模型的局限性。 将单细胞基因组学和生理学直接应用于人体组织位置的最新进展使我们的领域 通过改善临床翻译的机会，在疼痛生物学方面取得重要的新进展。人类 组织采购和加工核心将负责从验尸中获得高质量的组织 供体和慢性疼痛患者获得知情同意。 大多数形式的神经性疼痛的经验始于外周伤害者的异常点火 细胞体在背根神经节或三叉神经节中。这些神经节居住在中央紧张之外 如果可以选择性地抑制系统，并且可以制造理想的疼痛治疗靶标。因此，我们建议 从验尸中提取背根神经节，三叉神经节和远端坐骨神经，从验尸后人类供体使用 在马萨诸塞州综合医院建立了快速尸检计划。该IRB批准的协议已经 正在进行中，并从> 25个捐助者那里收集了样本，其中选择了成功处理 单核基因组测定。核心将基于这些已建立的组织采购和处理 协议与其他U19中心合作。 为了表征慢性疼痛患者的分子变化，患有慢性幻影的患者 症状性神经瘤继发于肌肉加剧手术期间将采用其神经瘤。 该协议已获得IRB批准，并且已经在注册中。新鲜和冷冻的样品将用于中心 单细胞基因组测定的研究者。 核心还将维持一个被识别的冷冻组织的组织库，以分配到中心研究人员 以及整个精确人类疼痛网络的研究人员。