Establishment of adult rat-derived stem cells, and histological/functional reconstruction of spinal cord by auto- and allo-grafting of those stem cells

基于早期的实验，我们认识到神经干细胞的临床应用还存在很大的障碍，即胚胎使用和不可避免的过敏性移植的伦理问题。另一方面，自体骨髓基质细胞（BMSCs）在临床应用上具有很大的优势。在实验中，将BMSCs通过大鼠的第四脑室注射到脑脊液（CSF）中。注射的骨髓间充质干细胞大量附着于脊髓表面，部分细胞进一步侵入病变区。根据BBB量表，细胞移植大鼠表现出14 15和11点的运动，而对照组分别为10和8点，在轻度和强烈的脊髓挤压，分别。脊髓腔大小约为100 mm。细胞移植组比对照组小1/2。与对照组相比，移植组大鼠星形胶质细胞增殖减少，神经成分保留较多，移植细胞消失 关于我们 注射后4-5周内从脊髓中排出艾德。这意味着注射的BMSCs不是通过整合到宿主组织中发挥作用，而是通过释放一些营养因子到CSF中发挥作用。体外实验也支持这一假设。骨髓间充质干细胞不是干细胞，而是来自成年动物的普通体细胞。认为BMSCs在退化的早期阶段抑制退化过程，同时促进受损细胞的存活。我们通过腰椎穿刺注射自体骨髓间充质干细胞，证实了骨髓间充质干细胞注射入猴脑脊液的安全性。我们提供了一个完整的临床应用方案，关西大学伦理委员会于2005年7月1日批准了通过骨髓间充质干细胞移植治疗脊髓损伤患者的脊髓治疗患者的细胞移植<st>。同时，我们还观察了脉络丛室管膜（上皮）细胞对缺血性脑损伤的影响，证实了注射培养的脉络丛室管膜细胞对缺血性脑损伤的恢复有很大的作用。这一发现可能为缺血性脑损伤的治疗开辟新的视野。少

Based on the early experiments, we recognized that there are big barriers for neural stem cells to be clinically applied : those are ethical problems concerning the use of fetus and inevitable allergenic transplantation. On the other hand, bone marrow stromal cells (BMSCs) have great advantages in being autogenic for clinical application. In experiments, BMSCs were injected into the cerebrospinal fluid (CSF) through the 4^th ventricle of the rat. Many injected BMSCs were attached to the spinal cord surface, and some of them further invaded the lesion. Based on the BBB scale, cell-graft rats showed 14 15 and 11 points in locomotion, while the controls were 10 and 8 points, in the mild and strong spinal cord crush, respectively. The size of spinal cord cavity was ca. 1/2 smaller in the cell-graft rats than the controls. Less proliferation of astrocytes was observed, and a larger amount of neural components was preserved in the cell-graft rats than in the controls.Injected cells disappear … More ed from the spinal cord within 4-5 weeks after injection. This implies that injected BMSCs exerted their effects not by being integrated into the host tissue, but by releasing some trophic factors into the CSF. The in vitro experiments also supported this hypothesis. BMSCs function not as stem cells, but as ordinary somatic cells derived from adult animals. It is considered that BMSCs suppress the degenerative processes, and at the same time promote the survival, of injured cells at the early stage of degeneration. We confirmed the safety of BMSC injection into the CSF in the monkey by injecting autogenic BMSCs through lumbar puncture. We provided a complete protocol for clinical application, and the Ethic Committee of Kansai University approved this cell transplantation to patients with spinal cord therapy by BMSC transplantation to patients with spinal cord injury on July 1^<st> 2005. We are now ready for the BMSC transplantation therapy to patients matched to the protocol.In parallel with this study, we also examined the effects of choroid plexus ependymal (epithelial) cells to the ischemic brain injury, and clarified that the injection of cultured choroid plexus ependymal cells have a great effect on the recovery of brain tissue from ischemic damages. This finding might open a new horizon for the therapy of ischemic brain injury. Less