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3D Printed Stem-Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds

机译:3D打印的干细胞衍生神经祖细胞产生脊髓支架

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摘要

A bioengineered spinal cord is fabricated via extrusion-based multimaterial 3D bioprinting, in which clusters of induced pluripotent stem cell (iPSC)-derived spinal neuronal progenitor cells (sNPCs) and oligodendrocyte progenitor cells (OPCs) are placed in precise positions within 3D printed biocompatible scaffolds during assembly. The location of a cluster of cells, of a single type or multiple types, is controlled using a point-dispensing printing method with a 200 mu m center-to-center spacing within 150 mu m wide channels. The bioprinted sNPCs differentiate and extend axons throughout microscale scaffold channels, and the activity of these neuronal networks is confirmed by physiological spontaneous calcium flux studies. Successful bioprinting of OPCs in combination with sNPCs demonstrates a multicellular neural tissue engineering approach, where the ability to direct the patterning and combination of transplanted neuronal and glial cells can be beneficial in rebuilding functional axonal connections across areas of central nervous system (CNS) tissue damage. This platform can be used to prepare novel biomimetic, hydrogel-based scaffolds modeling complex CNS tissue architecture in vitro and harnessed to develop new clinical approaches to treat neurological diseases, including spinal cord injury.
机译:通过基于挤压的多材料3D生物打印技术制造生物工程化的脊髓,其中将诱导多能干细胞(iPSC)衍生的脊髓神经元祖细胞(sNPC)和少突胶质祖细胞(OPC)的簇放置在3D打印的生物相容性内的精确位置组装过程中的脚手架。单点或多点细胞簇的位置是使用点分配打印方法控制的,该点分配打印方法在150微米宽的通道内的中心间距为200微米。生物印记的sNPCs可在整个微尺度支架通道中分化并扩展轴突,而这些神经元网络的活性已通过生理自发的钙通量研究得到了证实。 OPC与sNPC结合的成功生物印记证明了一种多细胞神经组织工程学方法,其中指导移植的神经元和神经胶质细胞的模式形成和结合的能力可能对重建中枢神经系统(CNS)组织损伤区域的功能性轴突连接有益。 。该平台可用于在体外制备新型的仿生,基于水凝胶的支架,以模拟复杂的中枢神经系统组织结构,并用于开发治疗包括脊髓损伤在内的神经系统疾病的新临床方法。

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