Human Tissue Procurement and Processing Core

人体组织采购和加工核心

基本信息

批准号：
10707433
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
项目类别：
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/10707433
关键词：
Agreement Animal Model Autopsy Biological Assay Biological Markers Biology Brain Cell Nucleus Cells Central Nervous System Chronic Collaborations Collection Data Databases Distal Drug or chemical Tissue Distribution Eligibility Determination Enrollment Freezing Ganglia General Hospitals Genetic Genomics Goals Human Individual Informed Consent Institutional Review Boards Knowledge Left Massachusetts Metadata Molecular Mus Nerve 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 Resolution 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

项目摘要

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，但小鼠的疼痛目标已经经历了几十年来，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。