Lai Bi-Qin, Feng Bo, Che Ming-Tian, Wang Lai-Jian, Cai Song, Huang Meng-Yao, Gu Huai-Yu, Jiang Bing, Ling Eng-Ang, Li Meng, Zeng Xiang, Zeng Yuan-Shan
Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University) Ministry of Education Guangzhou 510080 China.
Department of Histology and Embryology Zhongshan School of Medicine Sun Yat-sen University Guangzhou 510080 China.
Adv Sci (Weinh). 2018 Jul 20;5(9):1800261. doi: 10.1002/advs.201800261. eCollection 2018 Sep.
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.
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。在此,利用基于神经干细胞的组织工程技术,通过模拟脊髓的白质和灰质组成,在体外组装了一种生物工程可移植脊髓样组织(SCLT)。评估了该类器官是否会在损伤的脊髓中进行靶向修复。由白质样组织(WMLT)模块和灰质样组织(GMLT)模块组装而成的完整SCLT,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进行器官型共培养表明,SCLT分别具有脊髓器官发生潜力,可与靶标建立连接。将SCLT移植到横断的脊髓中可使大鼠瘫痪的后肢运动功能显著恢复。此外,SCLT的模块化设计实现了靶向脊髓组织修复,WMLT区域髓鞘再生增加和GMLT区域神经支配扩大证明了这一点。更重要的是,促再生微环境促进了供体神经元形成神经中继,使下行和上行神经输入得以传导。