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-

我们利用骨髓基质细胞（BMSCs）和脉络膜丛室管膜细胞（cpec）等具有临床应用潜力的细胞移植研究了脊髓再生。同种骨髓间充质干细胞于2006年3月23日通过腰椎穿刺注入脊髓损伤患者（C4,5）。这是首例骨髓间充质干细胞通过脑脊液（CSF）移植的脊髓损伤临床病例。该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，我们研究骨髓源性单核细胞在大鼠体内的移植，探讨脊髓损伤患者入院后立即进行细胞治疗而不进行任何细胞培养的可能性。大鼠脊髓空腔形成减少，运动能力改善。CFS中HGF浓度高，TNF-α浓度低。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从培养的骨髓间充质干细胞中发育出来的。实验表明，CPEC培养的条件培养基促进了神经元的存活，并在体外促进了神经突的延伸。在骨髓间充质干细胞的条件培养基中也观察到同样的效果。接下来，发现脉络膜丛室管膜细胞层含有神经干细胞。同样，第三脑室室管膜细胞层含有大量的神经干细胞。我们发现脊髓挤压损伤后，主要由中央椎管产生大量神经干细胞。同时，在病变部位促进bFGF的生成。为什么脊髓的这些变化不有助于脊髓再生的问题仍有待解决。

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.