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A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord
Advanced Science ( IF 15.1 ) Pub Date : 2018-07-20 , DOI: 10.1002/advs.201800261
Bi-Qin Lai 1, 2, 3 , Bo Feng 1 , Ming-Tian Che 1 , Lai-Jian Wang 4 , Song Cai 5 , Meng-Yao Huang 4 , Huai-Yu Gu 5 , Bing Jiang 4 , Eng-Ang Ling 6 , Meng Li 7 , Xiang Zeng 1, 2, 8 , Yuan-Shan Zeng 1, 2, 3, 4, 8
Affiliation  

Tissue engineering–based neural construction holds promise in providing organoids with defined differentiation and therapeutic potentials. Here, a bioengineered transplantable spinal cord–like tissue (SCLT) is assembled in vitro by simulating the white matter and gray matter composition of the spinal cord using neural stem cell–based tissue engineering technique. Whether the organoid would execute targeted repair in injured spinal cord is evaluated. The integrated SCLT, assembled by white matter–like tissue (WMLT) module and gray matter–like tissue (GMLT) module, shares architectural, phenotypic, and functional similarities to the adult rat spinal cord. Organotypic coculturing with the dorsal root ganglion or muscle cells shows that the SCLT embraces spinal cord organogenesis potentials to establish connections with the targets, respectively. Transplantation of the SCLT into the transected spinal cord results in a significant motor function recovery of the paralyzed hind limbs in rats. Additionally, targeted spinal cord tissue repair is achieved by the modular design of SCLT, as evidenced by an increased remyelination in the WMLT area and an enlarged innervation in the GMLT area. More importantly, the pro‐regeneration milieu facilitates the formation of a neuronal relay by the donor neurons, allowing the conduction of descending and ascending neural inputs.

中文翻译:

脊髓样组织的模块化组装允许在横断的脊髓中进行有针对性的组织修复

基于组织工程的神经构建有望为类器官提供明确的分化和治疗潜力。在这里,通过使用基于神经干细胞的组织工程技术模拟脊髓的白质和灰质组成,在体外组装了生物工程可移植脊髓样组织(SCLT)。评估类器官是否会对受伤的脊髓进行有针对性的修复。集成的 SCLT 由白质样组织 (WMLT) 模块和灰质样组织 (GMLT) 模块组装而成,在结构、表型和功能上与成年大鼠脊髓相似。与背根神经节或肌肉细胞的器官型共培养表明,SCLT 具有脊髓器官发生潜力,可分别与目标建立连接。将 SCLT 移植到横断的脊髓中可导致大鼠瘫痪后肢的运动功能显着恢复。此外,通过 SCLT 的模块化设计实现了有针对性的脊髓组织修复,WMLT 区域的髓鞘再生增加和 GMLT 区域的神经支配扩大就证明了这一点。更重要的是,促再生环境促进供体神经元形成神经元中继,从而允许传导下行和上行神经输入。
更新日期:2018-07-20
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