Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Brain Res. 2023 Oct 15;1817:148484. doi: 10.1016/j.brainres.2023.148484. Epub 2023 Jul 11.
Spinal cord injury (SCI) can cause paralysis with a high disease burden with limited treatment options. A single intravenous infusion of mesenchymal stem cells (MSCs) improves motor function in rat SCI models, possibly through the induction of axonal sprouting and remyelination. Repeated infusions (thrice at weekly intervals) of MSCs were administered to rats with chronic SCI to determine if multiple-dosing regimens enhance motor improvement. Chronic SCI rats were randomized and infused with vehicle (vehicle), single MSC injection at week 6 (MSC-1) or repeatedly injections of MSCs at 6, 7, and 8 weeks (MSC-3) after SCI induction. In addition, a single high dose of MSCs (HD-MSC) equivalent to thrice the single dose was infused at week 6. Locomotor function, light and electron microscopy, immunohistochemistry and ex vivo diffusion tensor imaging were performed. Repeated infusion of MSCs (MSC-3) provided the greatest functional recovery compared to single and single high-dose infusions. The density of remyelinated axons in the injured spinal cord was the greatest in the MSC-3 group, followed by the MSC-1, HD-MSC and vehicle groups. Increased sprouting of the corticospinal tract and serotonergic axon density was the greatest in the MSC-3 group, followed by MSC-1, HD-MSC, and vehicle groups. Repeated infusion of MSCs over three weeks resulted in greater functional improvement than single administration of MSCs, even when the number of infused cells was tripled. MSC-treated rats showed axonal sprouting and remyelination in the chronic phase of SCI.
脊髓损伤（SCI）可导致高疾病负担的瘫痪，且治疗选择有限。单次静脉输注间充质干细胞（MSCs）可改善大鼠 SCI 模型的运动功能，可能通过诱导轴突发芽和髓鞘再生。在慢性 SCI 大鼠中给予重复输注（每周间隔 3 次）MSCs，以确定多次给药方案是否增强运动改善。慢性 SCI 大鼠随机分组，给予载体（vehicle）、第 6 周单次 MSC 注射（MSC-1）或 SCI 诱导后第 6、7 和 8 周重复注射 MSCs（MSC-3）。此外，在第 6 周单次输注相当于三倍单次剂量的高剂量 MSCs（HD-MSC）。进行运动功能、光镜和电镜、免疫组织化学和离体扩散张量成像检查。与单次和单次高剂量输注相比，重复输注 MSCs（MSC-3）可提供最大的功能恢复。损伤脊髓中髓鞘化轴突的密度在 MSC-3 组最大，其次是 MSC-1、HD-MSC 和载体组。皮质脊髓束和 5-羟色胺能轴突密度的发芽增加在 MSC-3 组最大，其次是 MSC-1、HD-MSC 和载体组。在三周内重复输注 MSCs 比单次给予 MSCs 可获得更大的功能改善，即使输注细胞的数量增加了三倍。MSC 治疗的大鼠在 SCI 的慢性期表现出轴突发芽和髓鞘再生。
