理学療法ジャーナル39巻6号

2005年06月発行

プログレス

脊髄再生の可能性

著者： 岩波明生¹ 山根淳一¹ 加藤裕幸¹ 植田義之¹ 池上健¹ 石井賢¹ 小川祐人¹ 中村雅也¹ 戸山芳昭¹ 岡田誠司² 岡野栄之²

所属機関： ¹慶應義塾大学医学部整形外科 ²慶應義塾大学医学部生理学

ページ範囲：P.539 - P.546

20世紀初頭の著名な神経解剖学者であるRamon y Cajalが「ひとたび損傷を受けた中枢神経系の組織は二度と再生しない」と述べてから，中枢神経系の疾患や外傷で失われた機能の回復は不可能であるというのが通説であった．しかし近年の神経発生生物学の進歩により，中枢神経軸索の伸展制御の分子メカニズムや可塑性などが相次いで解明されはじめると同時に，中枢神経系にも自己複製能と多分化能を有した神経幹細胞の存在が明らかになり，中枢神経系の再生医学研究が非常に盛んになってきている．本稿では脊髄損傷に的を絞り，損傷脊髄の再生の可能性につき近年の研究成果を紹介しながら概説する．

脊髄損傷とは？

　脊髄損傷とは，交通事故や高所転落に伴う脊椎脱臼骨折などの外傷で脊髄実質が損傷されることにより，損傷部以下末梢の運動・知覚・自律神経系の麻痺を呈する病態のことである．現在本邦で約10万人，米国でも約25万人の患者がおり，年間本邦では5,000人，米国でも10,000人以上の患者が増加している．患者のほとんどが男性でしかも若年者が多く，近年医療の進歩に伴い受傷後も生存すること自体は十分可能となっているが，それだけに日常生活の不自由さや精神的な負担が長期間にわたり患者を苦しめる結果ともなり，社会的な問題となっている．

参考文献

1）Bracken MB, et al：Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA 277：1597-1604, 1997

2）Okada S, et al：Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury. J Neurosci Res 76：265-276, 2004

3）Brosamle C, et al：Regeneration of lesioned corticospinal tract fibers in the adult rat induced by a recombinant, humanized IN-1 antibody fragment. J Neurosci 20：8061-8068, 2000

4）Kikuchi K, et al：In vitro and in vivo characterization of a novel semaphorin 3A inhibitor, SM-216289 or xanthofulvin. J Biol Chem 278：42985-42991, 2003

5）Iwanami A, et al：Axonal regeneration by administration of Semaphorin3A inhibitor in the injured spinal cord. Abstract Viewer/Itinerary Planner. Washington, DC：Society for Neuroscience, CD-ROM. Program No. 775.6, 2003

6）Grill R, et al：Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial functional recovery after spinal cord injury. J Neurosci 17：5560-5572, 1997

7）Liu Y, et al：Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function. J Neurosci 19：4370-4387, 1999

8）Koda M, et al：Brain-derived neurotrophic factor suppresses delayed apoptosis of oligodendrocytes after spinal cord injury in rats. J Neurotrauma 19：777-785, 2002

9）Pincus DW, et al：Fibroblast growth factor-2/brain-derived neurotrophic factor-associated maturation of new neurons generated from adult human subependymal cells. Ann Neurol 43：576-585, 1998

10）Frisen J, et al：Rapid, widespread, and longlasting induction of nestin contributes to the generation of glial scar tissue after CNS injury. J Cell Biol 131：453-464, 1995

11）Nakamura M, et al：Differences in cytokine expression profile between acute and secondary injury in adult rat spinal cord. Exp Neurol 184：313-325, 2003

12）Ogawa Y, et al：Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats. J Neurosci Res 69：925-933, 2002

13）Iwanami A, et al：Establishment of graded spinal cord injury model in a non-human primate：the common marmoset. J Neurosci Res 80：172-181, 2005

14）Iwanami A, et al：Transplantation of human neural stem cells for spinal cord injury in primates. J Neurosci Res 80：182-190, 2005

15）Aguayo A, et al：Influences of the glial environment on the elongation of axons after injury：transplantation studies in adult rodents. J Exp Biol 95：231-240, 1981

16）Bregman BS, et al：Recovery of function after spinal cord injury：mechanisms underlying transplant-mediated recovery of function differ after spinal cord injury in newborn and adult rats. Exp Neurol 123：3-16, 1993

17）McDonald JW, et al：Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med 5：1410-1412, 1999

18）Li Y, et al：Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 277：2000-2002, 1997

19）Ramon-Cueto A, et al：Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron 25：425-435, 2000

20）Barnett SC, et al：Olfactory ensheathing cells and CNS repair：going solo or in need of a friend?Trends Neurosci 27：54-60, 2004

21）Huang H, et al：Influence of patients'age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury. Chin Med J 116：1488-1491, 2003

22）Hofstetter CP, et al：Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci USA 99：2199-2204, 2002

23）Saporta S, et al：Human umbilical cord blood stem cells infusion in spinal cord injury：engraftment and beneficial influence on behavior. J Hematother Stem Cell Res 12：271-278, 2003

24）Mikami Y, et al：Implantation of dendritic cells in injured adult spinal cord results in activation of endogenous neural stem/progenitor cells leading to de novo neurogenesis and functional recovery. J Neurol Res 76：453-465, 2004

25）Bareyre FM, et al：The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat Neurosci 7：269-277, 2004

26）Roy RR, et al：Training effects on soleus of cats spinal cord transected（T12-13）as adults. Muscle Nerve 21：63-71, 1998

27）Timoszyk WK, et al：The rat lumbosacral spinal cord adapts to robotic loading applied during stance. J Neurophysiol 88：3108-3117, 2002

28）Hornby TG, et al：Robotic-assisted, body-weight-supported treadmill training in individuals following motor incomplete spinal cord injury. Phys Ther 85：52-66, 2005

29）Kern H, et al：Long-term denervation in humans causes degeneration of both contractile and excitation-contraction coupling apparatus, which is reversible by functional electrical stimulation（FES）：a role for myofiber regeneration?J Neuropathol Exp Neurol 63：919-931, 2004