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: 10840561
• 负责人: Ann M Parr
• 金额: $ 7.43万
• 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/10840561
• 关键词: 3-Dimensional; 3D Print; Adult; Biocompatible Materials; Cell Transplantation; Cells; Chronic; Electrophysiology (science); Goals; Histologic; Human; Injury; Knowledge; Modeling; Neurons; Organoids; Patients; Persons; Public Health; Rattus; Recovery of Function; Research; Site; Spinal; Spinal Cord; Spinal cord injury; System; Testing; Translating; Transplantation; Vertebral column; bench to bedside; bioink; bioprinting; combinatorial; design; effective therapy; injured; nerve stem cell; neurotransmission; next generation; scaffold; 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的作用机制 慢性脊髓损伤（SCI）的移植疗法，并将这些知识转化为 为患者提供长凳到床边。人类SCI目前尚无有效的治疗方法，任何新的治疗方法 治疗将对公众健康产生重大影响。本次活动的总体目标 建议确定是否可以移植区域特异性生物打印脊髓神经 祖细胞 (sNPC) 与 3D 打印支架相结合可导致形成 受伤的成年大鼠脊髓内的功能性神经元网络。我们有三个具体的 目标。第一个目标是优化 3D 打印支架的生物材料和设计 作为生物打印中使用的充满细胞的生物墨水。第二个目标是确定最佳小区 在支架内配置两种类型的区域特异性 sNPC 以形成功能性 神经元网络。第三个目标是在大鼠横断损伤模型中测试我们的支架 确定我们的细胞是否可以在受伤部位提供中继系统，以及是否 这将导致功能恢复。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。这 科学前提是在提供基质（细胞）方面存在协同关系 跨损伤部位的中继系统，并通过导管（支架）对其进行优化，提供 神经信号的有效中继导致功能恢复。

项目成果

Cell Transplantation for Repair of the Spinal Cord and Prospects for Generating Region-Specific Exogenic Neuronal Cells.

用于修复脊髓的细胞移植和生成区域特异性外源神经元细胞的前景。

• 发表时间: 2024
• 影响因子: 3.3
• 作者: Roman, Ale;Huntemer;Waldron, Madison A;Khalid, Zainab;Blake, Jeffrey;Parr, Ann M;Low, Walter C
• 通讯作者: Low, Walter C

Accelerated differentiation of human induced pluripotent stem cells into regionally specific dorsal and ventral spinal neural progenitor cells for application in spinal cord therapeutics.

人类诱导多能干细胞加速分化为区域特异性背侧和腹侧脊髓神经祖细胞，用于脊髓治疗。

• 发表时间: 2023
• 作者: Huntemer-Silveira, Anne;Malone, Dane;Frie, Anna;Walsh, Patrick;Parr, Ann M.
• 通讯作者: Parr, Ann M.