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Regenerative medicine for spinal cord injury using induced pluripotent stem cells: from animals to humans.
Pain ( IF 5.9 ) Pub Date : 2024-11-01 , DOI: 10.1097/j.pain.0000000000003306
Narihito Nagoshi,Shogo Hashimoto,Hideyuki Okano,Masaya Nakamura

Spinal cord injury (SCI) results in permanent neurological dysfunction and neuropathic pain. To address this pathology, we recently conducted a clinical study in which we transplanted neural precursor cells (NPCs) derived from human induced pluripotent stem cells into patients during the subacute phase of SCI. One of the therapeutic mechanisms of cell transplantation is the formation of synaptic connections with the host's neural tissues, which we demonstrated using a chemogenetic tool. In addition, we have developed innovative strategies to enhance the effectiveness of cell transplantation through gene therapy. Moreover, our current study is focused on developing cell therapy for chronic SCI, a more challenging pathology characterized by the formation of cavities and scar tissue. In such situations, transplanting NPCs with neurogenic properties could effectively penetrate scar tissue and form functional synapses with the host neurons. To improve the outcomes of cell transplantation alone, we have found that incorporating rehabilitation is beneficial. In animal models of SCI, we have established an effective rehabilitative training program in which NPCs were transplanted during the chronic phase. Robotic rehabilitation has demonstrated improvements in gait ability and trunk function in clinical situations. Therefore, regenerative medicine shows promise for chronic SCI, particularly when rehabilitation strategies are incorporated.

中文翻译:


使用诱导多能干细胞治疗脊髓损伤的再生医学:从动物到人类。



脊髓损伤 (SCI) 导致永久性神经功能障碍和神经性疼痛。为了解决这种病理问题,我们最近进行了一项临床研究,在这项研究中,我们将源自人诱导多能干细胞的神经前体细胞 (NPC) 移植到 SCI 亚急性期的患者体内。细胞移植的治疗机制之一是与宿主的神经组织形成突触连接,我们使用化学遗传学工具证明了这一点。此外,我们还开发了创新策略,通过基因治疗提高细胞移植的有效性。此外,我们目前的研究重点是开发针对慢性 SCI 的细胞疗法,慢性 SCI 是一种更具挑战性的病理,其特征是形成空腔和疤痕组织。在这种情况下,具有神经源性特性的移植 NPC 可以有效地穿透疤痕组织并与宿主神经元形成功能性突触。为了改善单独细胞移植的结局,我们发现结合康复是有益的。在 SCI 的动物模型中,我们建立了一个有效的康复训练计划,其中 NPC 在慢性期被移植。机器人康复已证明在临床情况下步态能力和躯干功能有所改善。因此,再生医学显示出治疗慢性 SCI 的前景,尤其是在纳入康复策略时。
更新日期:2024-11-01
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