Department of Neurosurgery, Graduate School of Medicine, Tohoku University, Sendai 980-8572, Japan.
Department of Neurosurgery, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan.
Int J Mol Sci. 2023 Sep 27;24(19):14603. doi: 10.3390/ijms241914603.
Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.
多能性成体祖细胞（Muse）是新建立的多能干细胞。本研究旨在探讨全身给予 Muse 细胞作为亚急性脊髓损伤（SCI）有效治疗方法的潜力。我们在中胸段脊髓挫伤后两周，通过静脉给予含有 Muse 细胞的临床产品“CL2020”。8 只实验动物接受了 CL2020，12 只接受了载体。在 20 周的时间里进行了行为分析。进行了组织学评估。在观察 20 周后，用白喉毒素处理了 3 只接受 CL2020 治疗的动物，以选择性地消除人细胞功能。CL2020 给药后 6 至 20 周，后肢运动功能显著改善。CL2020 组的囊腔较小。此外，在脊髓远端保存了更多的下行 5-HT 纤维。CL2020 中的 Muse 细胞被认为已分化为损伤脊髓中的神经元和神经细胞。神经元和神经细胞分别在灰质和白质中被鉴定出来。重要的是，这些作用通过白喉毒素对人细胞的选择性消除而逆转。静脉给予 Muse 细胞促进了 CL2020 对严重亚急性脊髓损伤的治疗潜力。
