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

基本信息

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
项目类别：
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

项目摘要

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的作用机制慢性脊髓损伤（SCI）的移植疗法，并从病人的长凳。人类SCI目前没有有效的治疗方法，任何新的治疗将对公共卫生产生重大影响。总体目标建议是确定是否对区域特异性生物打印的脊柱神经移植祖细胞（SNPC）与3D印刷支架结合使用会导致形成受伤的成年大鼠脊髓中的功能性神经元网络。我们有三个特定的目标。第一个目的是优化3D印刷脚手架的生物材料和设计作为载有细胞的生物墨水用于生物打印。第二个目的是确定最佳单元格支架内两种类型的区域特定SNPC的配置以形成功能神经元网络。第三个目的是测试我们的脚手架在大鼠的横断损伤模型中测试确定我们的细胞是否可以在伤害部位提供继电器系统，以及是否可以这将导致功能恢复。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。这科学的前提是，在提供底物（Cell）的底物（单元）方面存在协同关系跨伤害地点的中继系统，并用导管（脚手架）优化它，提供神经元信号传导的有效继电器导致功能恢复。