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（人体组织采购和处理核心） 尽管我们对动物模型伤害感受的理解取得了进展，但小鼠的疼痛目标却经历了 几十年来，在将慢性疼痛患者的新型有效且安全的治疗方法转化为新的有效且安全的治疗方法方面遇到了困难。缺乏 小鼠和人类疼痛治疗之间的转化凸显了疼痛动物模型的局限性。 将单细胞基因组学和生理学直接应用于人体组织的最新进展使我们的领域能够 在疼痛生物学方面取得重要的新进展，并改善临床转化的机会。人类 组织采购和处理核心将负责从尸检中获取高质量的组织 捐赠者和慢性疼痛患者知情同意。 大多数形式的神经性疼痛的经历始于外周伤害感受器的异常放电，其 细胞体位于背根神经节或三叉神经节。这些神经节位于中枢神经之外 如果可以选择性地抑制它们，则将成为理想的疼痛治疗靶点。因此我们建议 使用死后人类捐赠者提取背根神经节、三叉神经节和远端坐骨神经 在马萨诸塞州总医院建立了快速尸检计划。该协议已获得 IRB 批准 正在进行中，并已从超过 25 名捐赠者那里收集了样本，其中一些样本已成功处理用于 单核基因组分析。核心将建立在这些已建立的组织采购和加工基础上 与其他 U19 中心合作的协议。 为了表征慢性疼痛患者、慢性幻肢患者发生的分子变化 继发于有症状的神经瘤将在肌肉神经支配手术期间获得神经瘤。 该协议已获得 IRB 批准并已在注册。新鲜和冷冻样品将提供给中心 单细胞基因组分析的研究人员。 核心还将维护一个包含未识别身份的冷冻组织的组织库，以分发给中心研究人员 以及 PRECISION Human Pain Network 的研究人员。