Promotion of brain-and spinal-cord regeneration by transplantation of somatic cells(bone marrow stromal cells and choroid plexus ependymal cells)-mechanisms of rescuing injured neural cells, and perspectives for clinical applications-

我们研究了通过细胞移植进行脊髓再生的方法，这些细胞具有潜在的临床应用价值，例如骨髓基质细胞（BMSCs）和脉络丛室管膜细胞（CPECs）. 2006年3月23日，通过腰椎穿刺将自体BMSCs注射到脊髓损伤患者（C4，5）中。这是第一例通过脑脊液（CSF）移植骨髓间充质干细胞的脊髓损伤的临床病例。患者尚未出现有害的副作用，同时显示出功能改善的迹象。接下来，我们研究了骨髓来源的单核细胞在大鼠中的移植，以探索在入院后立即对脊髓损伤患者进行细胞治疗而无需任何细胞培养过程的可能性。大鼠显示脊髓中的空腔形成减少，并且运动改善。CFS中HGF含量高，TNF-α含量低。腔壁可见大量血管和神经纤维。这些再生效应被认为是由于单个核细胞分泌的营养因子。接下来，我们发现许多骨骼肌细胞是由培养的BMSC发育而来的。CPEC条件培养液能促进体外培养的神经元的存活和突起的生长。骨髓间充质干细胞条件培养液也有同样的作用。接下来，揭示了脉络丛室管膜细胞层包含神经干细胞。同样，第三脑室室管膜细胞层含有大量的神经干细胞.我们发现脊髓挤压伤后大量的神经干细胞主要来源于中央管。同时，bFGF的产生促进了病变。为什么脊髓的这些变化对脊髓再生没有贡献的问题仍有待解决。

We studied spinal cord regeneration by cell transplantation using those cells that are potentially available for clinical application, such as bone marrow stromal cells (BMSCs) and choroid plexus ependymal cells (CPECs).1. BMSCsAutogeneous BMSCs were injected by lumbar puncture to a patient with spinal cord injury (C4,5) on March 23, 2006. This is the first clinical case of spinal cord injury in which BMSCs were transplanted through cerebrospinal fluid (CSF). The patient has as yet had no harmful side effect, while showing a sign of functional improvement. Next, we studied transplantation of bone marrow-derived mononuclear cells in the rat to explore the possibility of cell therapy without any cell culture process for spinal cord-injured patients immediately after admission to the hospital. The rat showed the reduced cavity formation in the spinal cord, and improved locomotion. HGF was high, and TNF-α was low in concentration in the CFS. A large number of blood vessels and nerve fibers were seen in the cavity wall. These regenerative effects are considered due to trophic factors secreted from mononuclear cells.Next, we discovered that many skeletal muscle cells develop from cultured BMSCs.2. CPECsWe showed that conditioned medium of CPEC culture promotes the survival of neurons, and neurite extension in vitro. The same effects were seen with the conditioned medium of BMSCs. Next, it was revealed that the choroid plexus ependymal cell layer contains neural stem cells. Similarly, the third ventricle ependymal cell layer contains a large number of neural stem cells.3. OthersWe showed that a large number of neural stem cells are generated mainly from central canal following crush injury to the spinal cord. At the same time, bFGF production was promoted in the lesion. The question of why these changes of spinal cord do not contribute to the spinal cord regeneration remains to be resolved.