Ogawa Y, Sawamoto K, Miyata T, Miyao S, Watanabe M, Nakamura M, Bregman B S, Koike M, Uchiyama Y, Toyama Y, Okano H
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
J Neurosci Res. 2002 Sep 15;69(6):925-33. doi: 10.1002/jnr.10341.
Neural progenitor cells, including neural stem cells, are a potential expandable source of graft material for transplantation aimed at repairing the damaged CNS. Here we present the first evidence that in vitro-expanded fetus-derived neurosphere cells were able to generate neurons in vivo and improve motor function upon transplantation into an adult rat spinal-cord-contusion injury model. As the source of graft material, we used a neural stem cell-enriched population that was derived from rat embryonic spinal cord (E14.5) and expanded in vitro by neurosphere formation. Nine days after contusion injury, these neurosphere cells were transplanted into adult rat spinal cord at the injury site. Histological analysis 5 weeks after the transplantation showed that mitotic neurogenesis occurred from the transplanted donor progenitor cells within the adult rat spinal cord, a nonneurogenic region; that these donor-derived neurons extended their processes into the host tissues; and that the neurites formed synaptic structures. Furthermore, analysis of motor behavior using a skilled reaching task indicated that the treated rats showed functional recovery. These results indicate that in vitro-expanded neurosphere cells derived from the fetal spinal cord are a potential source for transplantable material for treatment of spinal cord injury.
神经祖细胞，包括神经干细胞，是一种具有潜在可扩展性的移植材料来源，可用于旨在修复受损中枢神经系统的移植。在此，我们首次证明，体外扩增的胎儿来源神经球细胞能够在体内生成神经元，并在移植到成年大鼠脊髓挫伤损伤模型后改善运动功能。作为移植材料的来源，我们使用了富含神经干细胞的群体，该群体来源于大鼠胚胎脊髓（E14.5），并通过神经球形成在体外进行扩增。挫伤损伤9天后，将这些神经球细胞移植到成年大鼠脊髓的损伤部位。移植后5周的组织学分析表明，在成年大鼠脊髓（一个非神经发生区域）内，移植的供体祖细胞发生了有丝分裂神经发生；这些供体来源的神经元将其突起延伸到宿主组织中；并且神经突形成了突触结构。此外，使用熟练抓握任务对运动行为进行的分析表明，接受治疗的大鼠显示出功能恢复。这些结果表明，来自胎儿脊髓的体外扩增神经球细胞是治疗脊髓损伤的潜在可移植材料来源。
