Abstract：
BACKGROUND: Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI.
METHODS: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo.
RESULTS: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery.
CONCLUSIONS: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.
METHODS: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo.
RESULTS: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery.
CONCLUSIONS: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.
摘要：
背景：脊髓损伤（SCI）是一种破坏性疾病，可引起少突胶质细胞和神经元的广泛损伤，导致脱髓鞘和轴突变性。在这项研究中,我们共移植了包含来自人诱导多能干细胞（iPSCs）的少突胶质细胞祖细胞（OPCs）与人脐静脉内皮细胞（HUVECs）的细胞移植物，据报道，它们促进了OPCs的生存和迁移，入大鼠挫伤模型以促进SCI后功能恢复。
方法：OPCs来自iPSCs，并在不同时间点通过免疫荧光进行鉴定。进行体外功能测定以评估HUVECs对增殖的影响。迁移,以及通过共培养和迁移测定OPCs的存活，以及神经元轴突的生长。将OPCs和HUVEC的组合移植到大鼠挫伤模型中。8周后,免疫荧光染色检测移植细胞的安全性,观察神经元修复情况,髓鞘形成,和受伤区域的神经回路重建；功能恢复由Basso评估，Beattie,和Bresnahan开放领域规模，爬梯,SEP,MEP。此外，HUVECs对移植物的影响也在体内测定。
结果：数据显示HUVECs促进其增殖，迁移,和OPCs在体外和体内的存活。此外，植入后8周，OPCs和HUVECs共同移植的大鼠明显促进了髓鞘再生，增强移植物与宿主之间的功能连接，促进功能恢复。此外,与OPCs单独移植相比，共同移植在病变边界产生了更多的感觉神经元，并显着改善了感觉功能恢复。
结论：我们的研究表明，OPCs联合HUVEC移植可显著提高SCI后的运动和感觉功能恢复。OPCs联合HUVECs组和OPCs单独组的运动功能恢复无显著性,OPCs联合HUVECs组的感觉功能恢复明显优于其他两组。这些发现为SCI研究领域提供了新的见解。
方法：OPCs来自iPSCs，并在不同时间点通过免疫荧光进行鉴定。进行体外功能测定以评估HUVECs对增殖的影响。迁移,以及通过共培养和迁移测定OPCs的存活，以及神经元轴突的生长。将OPCs和HUVEC的组合移植到大鼠挫伤模型中。8周后,免疫荧光染色检测移植细胞的安全性,观察神经元修复情况,髓鞘形成,和受伤区域的神经回路重建；功能恢复由Basso评估，Beattie,和Bresnahan开放领域规模，爬梯,SEP,MEP。此外，HUVECs对移植物的影响也在体内测定。
结果：数据显示HUVECs促进其增殖，迁移,和OPCs在体外和体内的存活。此外，植入后8周，OPCs和HUVECs共同移植的大鼠明显促进了髓鞘再生，增强移植物与宿主之间的功能连接，促进功能恢复。此外,与OPCs单独移植相比，共同移植在病变边界产生了更多的感觉神经元，并显着改善了感觉功能恢复。
结论：我们的研究表明，OPCs联合HUVEC移植可显著提高SCI后的运动和感觉功能恢复。OPCs联合HUVECs组和OPCs单独组的运动功能恢复无显著性,OPCs联合HUVECs组的感觉功能恢复明显优于其他两组。这些发现为SCI研究领域提供了新的见解。
