Jin Chen, Wu Yayu, Zhang Haipeng, Xu Bai, Liu Wenbin, Ji Chunnan, Li Panpan, Chen Zhenni, Chen Bing, Li Jiayin, Wu Xianming, Jiang Peipei, Hu Yali, Xiao Zhifeng, Zhao Yannan, Dai Jianwu
University of the Chinese Academy of Sciences Beijing China.
State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology, Chinese Academy of Sciences Beijing China.
Bioeng Transl Med. 2022 Nov 9;8(2):e10448. doi: 10.1002/btm2.10448. eCollection 2023 Mar.
Neural progenitor cell (NPC) transplantation is a promising approach for repairing spinal cord injury (SCI). However, cell survival, maturation and integration after transplantation are still major challenges. Here, we produced a novel centimeter-scale human spinal cord neural tissue (hscNT) construct with human spinal cord neural progenitor cells (hscNPCs) and human spinal cord astrocytes (hscAS) on a linearly ordered collagen scaffold (LOCS). The hscAS promoted hscNPC adhesion, survival and neurite outgrowth on the LOCS, to form a linearly ordered spinal cord-like structure consisting of mature neurons and glia cells. When transplanted into rats with SCI, the hscNT created a favorable microenvironment by inhibiting inflammation and glial scar formation, and promoted neural and vascular regeneration. Notably, the hscNT promoted neural circuit reconstruction and motor functional recovery. Engineered human spinal cord implants containing astrocytes and neurons assembled on axon guidance scaffolds may therefore have potential in the treatment of SCI.
神经祖细胞(NPC)移植是修复脊髓损伤(SCI)的一种很有前景的方法。然而,移植后细胞的存活、成熟和整合仍然是主要挑战。在此,我们在线性有序胶原支架(LOCS)上,用人脊髓神经祖细胞(hscNPCs)和人脊髓星形胶质细胞(hscAS)构建了一种新型的厘米级人脊髓神经组织(hscNT)。hscAS促进hscNPC在LOCS上的黏附、存活和神经突生长,形成由成熟神经元和神经胶质细胞组成的线性有序脊髓样结构。当移植到脊髓损伤大鼠体内时,hscNT通过抑制炎症和胶质瘢痕形成创造了有利的微环境,并促进神经和血管再生。值得注意的是,hscNT促进了神经回路重建和运动功能恢复。因此,在轴突导向支架上组装有星形胶质细胞和神经元的工程化人脊髓植入物可能在脊髓损伤治疗中具有潜力。