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

项目摘要/摘要 这项研究的长期目标是确定成功的细胞移植的作用机制。 治疗慢性脊髓损伤(SCI)，并为患者将这一知识从板凳转化到床边。 人类脊髓损伤目前还没有有效的治疗方法，任何新的治疗方法都将对 公共卫生。这项提案的总体目标是确定是否有地区性特定的 生物打印的脊髓神经前体细胞(SNPC)与3D打印支架相结合可以导致 损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，以及细胞生物墨水 用于生物印刷。第二个目标是确定两种区域类型的最优小区配置 支架内特定的sNPC形成功能神经元网络。第三个目标是在 建立大鼠横断损伤模型，以确定我们的细胞是否能提供跨越损伤部位的中继系统， 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 电生理分析，以阐明我们的联合治疗的机制。科学的 前提是在为跨区域的中继系统提供基板(单元)时存在协同关系 损伤部位，并使用管道(支架)进行优化，为神经元信号传导提供有效的继电器 为功能恢复干杯。

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.