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.

项目摘要/摘要 这项研究的长期目标是定义成功细胞移植的作用机理 治疗慢性脊髓损伤（SCI），并将这些知识从长凳转化为患者的床边。 人类SCI目前没有有效的治疗方法，任何新疗法都会对 公共卫生。该提案的总体目的是确定是否对区域特定的移植 生物打印的脊柱神经祖细胞（SNPC）与3D印刷脚手架结合 受伤的成年大鼠脊髓中功能性神经元网络的形成。我们有三个具体的目标。 第一个目的是优化3D印刷脚手架的生物材料和设计以及富含细胞的生物学 用于生物打印。第二个目的是确定两种区域类型的最佳单元格配置 支架内的特定SNPC形成功能性神经元网络。第三个目的是测试我们的脚手架 大鼠的横切损伤模型，以确定我们的细胞是否可以在整个损伤部位提供继电器系统， 以及这是否会导致功能恢复。我们将执行详细的功能，组织学和 电生理分析以阐明我们联合治疗的机制。科学 前提是在为中继系统提供基板（单元）时存在协同关系 损伤部位并用导管（支架）优化它，为神经元信号引导提供了有效的继电器 进行功能恢复。