Kadoya Ken, Lu Paul, Nguyen Kenny, Lee-Kubli Corinne, Kumamaru Hiromi, Yao Lin, Knackert Joshua, Poplawski Gunnar, Dulin Jennifer N, Strobl Hans, Takashima Yoshio, Biane Jeremy, Conner James, Zhang Su-Chun, Tuszynski Mark H
Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Department of Orthopaedic Surgery, Hokkaido University, Sapporo, Japan.
Nat Med. 2016 May;22(5):479-87. doi: 10.1038/nm.4066. Epub 2016 Mar 28.
The corticospinal tract (CST) is the most important motor system in humans, yet robust regeneration of this projection after spinal cord injury (SCI) has not been accomplished. In murine models of SCI, we report robust corticospinal axon regeneration, functional synapse formation and improved skilled forelimb function after grafting multipotent neural progenitor cells into sites of SCI. Corticospinal regeneration requires grafts to be driven toward caudalized (spinal cord), rather than rostralized, fates. Fully mature caudalized neural grafts also support corticospinal regeneration. Moreover, corticospinal axons can emerge from neural grafts and regenerate beyond the lesion, a process that is potentially related to the attenuation of the glial scar. Rat corticospinal axons also regenerate into human donor grafts of caudal spinal cord identity. Collectively, these findings indicate that spinal cord 'replacement' with homologous neural stem cells enables robust regeneration of the corticospinal projection within and beyond spinal cord lesion sites, achieving a major unmet goal of SCI research and offering new possibilities for clinical translation.
皮质脊髓束（CST）是人类最重要的运动系统，但脊髓损伤（SCI）后该投射的强大再生尚未实现。在SCI的小鼠模型中，我们报告了将多能神经祖细胞移植到SCI部位后，皮质脊髓轴突的强大再生、功能性突触形成以及熟练前肢功能的改善。皮质脊髓再生需要将移植物导向尾侧化（脊髓）而非头侧化的命运。完全成熟的尾侧化神经移植物也支持皮质脊髓再生。此外，皮质脊髓轴突可以从神经移植物中穿出并在损伤部位以外再生，这一过程可能与胶质瘢痕的减弱有关。大鼠皮质脊髓轴突也能再生进入具有尾侧脊髓特征的人类供体移植物。总体而言，这些发现表明，用同源神经干细胞“替换”脊髓能够使皮质脊髓投射在脊髓损伤部位内外实现强大再生，实现了SCI研究一个主要的未满足目标，并为临床转化提供了新的可能性。
