3D Bioprinted Spinal Cord Organoids as a Relay System for Spinal Cord Injury

3D 生物打印脊髓类器官作为脊髓损伤的中继系统

• 批准号: 10296712
• 负责人: Ann M Parr
• 金额: $ 44.29万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-02 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10296712
• 关键词: 3-Dimensional; 3D Print; Acute; Address; Adult; Attention; Axon; Biocompatible Materials; Cell Maturation; Cell Survival; Cell Transplantation; Cells; Chronic; Cicatrix; Complex; Contusions; Custom; Dimensions; Dorsal; Electrophysiology (science); Future; Goals; Histologic; Human; In Vitro; Injury; Knowledge; Lead; Lesion; Location; Methods; Modeling; Natural regeneration; Neurons; Organoids; Patients; Population; Process; Public Health; Publishing; Rattus; Recovery of Function; Reporting; Research; Rodent; Rodent Model; Site; Specificity; Spinal; Spinal Cord; Spinal cord injury; Synapses; System; Testing; Translating; Translations; Transplantation; United States; Work; axon guidance; behavioral study; bench to bedside; bioprinting; cell type; clinically relevant; combinatorial; design; effective therapy; improved; in vivo; induced pluripotent stem cell; injured; nerve stem cell; neural circuit; neural network; neuron development; neurotransmission; next generation; novel; regenerative approach; relating to nervous system; scaffold; stem; stem cells; transplantation therapy

PROJECT SUMMARY/ABSTRACT The long-term goal of this research is to define the mechanisms of action of a successful cell transplantation therapy for chronic spinal cord injury (SCI) and to translate this knowledge from bench to bedside for patients. Human SCI currently has no effective treatment, and any new treatments would have a significant impact on public health. The overall objective of this proposal is to determine whether transplantation of regionally specific bioprinted spinal neural progenitor cells (sNPCs) in combination with a 3D printed scaffold can result in the formation of functional neuronal networks within the injured adult rat spinal cord. We have three specific aims. The first aim is to optimize the biomaterial and design of the 3D printed scaffold, as well as the cell-laden bioink utilized in bioprinting. The second aim is to determine the optimal cell configuration of two types of regionally specific sNPCs within the scaffold to form functional neuronal networks. The third aim is to test our scaffold in a rat model of transection injury to determine whether our cells can provide a relay system across the site of injury, and whether this will result in functional recovery. We will perform detailed functional, histological, and electrophysiological analyses to elucidate the mechanisms of our combinatorial treatment. The scientific premise is that there is a synergistic relationship in providing the substrate (cells) for a relay system across the injury site and optimizing this with a conduit (scaffold), providing an effective relay for neuronal signaling leading to functional recovery.

项目概要/摘要 这项研究的长期目标是确定成功细胞移植的作用机制 慢性脊髓损伤 (SCI) 的治疗，并将这些知识从实验室转化为患者的临床。 人类SCI目前尚无有效的治疗方法，任何新的治疗方法都会对 公共卫生。该提案的总体目标是确定是否可以移植区域特定的 生物打印的脊髓神经祖细胞 (sNPC) 与 3D 打印支架相结合可以产生 受伤的成年大鼠脊髓内功能性神经元网络的形成。我们有三个具体目标。 第一个目标是优化 3D 打印支架的生物材料和设计，以及充满细胞的生物墨水 用于生物打印。第二个目标是确定两种类型区域的最佳小区配置 支架内的特定 sNPC 形成功能性神经元网络。第三个目标是测试我们的脚手架 横断损伤的大鼠模型，以确定我们的细胞是否可以在损伤部位提供中继系统， 以及这是否会导致功能恢复。我们将进行详细的功能、组织学和 电生理学分析以阐明我们的组合治疗机制。科学的 前提是在为中继系统提供基质（细胞）方面存在协同关系 损伤部位并通过导管（支架）对其进行优化，为神经信号传导提供有效的中继 到功能恢复。