It has been believed as true since famous neurological scientist Ramon Y Cajal stated that ‘damage to the central nerve system of mammalians never recover from its total damage’. Injury to the spinal cord results in loss of sensory, motor and autonomic nerve function, and there is NO effective treatment to the complete spinal cord injury. We have reported efficacy of cell transplantation using iPS cells (induced pluripotent stem cells, developed by Dr. Shinya Yamanaka) derived neural stem cells on treatment of the spinal cord injury of non-human primate, such as common marmosets. We also develop novel imaging protocols for the central nervous system such as DTT (diffusion tensor tractgraphy) which enables us to investigate spinal cord regeneration non-invasively and precisely.
Masaya Nakamura, MD
Clinical fact of complete spinal cord injury, a case of 18 years old male.
There was no functional recovery following fusion surgery of C5 and C6.
Cell transplantation of human neural stem cells to spinal cord injury of common marmosets
Significant functional recovery has been observed in cell transplanted common marmosets.
Treatment of spinal cord injury by neural stem cells induced from human iPS cells
We successfully induced neural stem cells from human iPS cells, and showed its efficacy of cell transplantation on spinal cord injury of the mice.
Advance in spinal cord injury imaging
We developed DTT to visualize recovery of the nerve system from spinal cord injury, and applied it to evaluate effect of the treatment.
DTT of normal spinal cord (upper low) and that following hemisection to the spinal cord.
Rehabilitation to accelerate recovery from spinal cord injury
We found several factors to reduce scar formation around the injured site and developed animal model to evaluate rehabilitation following spinal cord injury.
Iida T, Nakamura M, Tsuji O, Iwanami A, Mikami S, Toyama Y, Chiba K, Matsumoto M. Dumbbell mesenchymal chondrosarcoma: report of a rare case. J Orthop Sci. 19: 190-193, 2014 Jan. (1.008)
Shinozaki M, Nakamura M, Konomi T, Kobayashi Y, Takano M, Saito N, Toyama Y, Okano H. Distinct roles of endogenous vascular endothelial factor receptor 1 and 2 in neural protection after spinal cord injury. Neurosci Res. 78: 55-64, 2014 Jan. (2.145)
Takano M, Kawabata S, Komaki Y, Shibata S, Hikishima K, Toyama Y, Okano H, Nakamura M. Inflammatory cascades mediate synapse elimination in spinal cord compression. J Neuroinflammation. 11: 40, 2014 Mar. (4.902)
Zhang L, Kaneko S, Kikuchi K, Sano A, Maeda M, Kishino A, Shibata S, Mukaino M, Toyama Y, Liu M, Kimura T, Okano H, Nakamura M. Rewiring of regenerated axons by combining treadmill training with semaphorin3A inhibition. Mol Brain. 7: 14, 2014 Mar. (4.345)
Nakamura M, Nishiwaki Y, Ushida T, Toyama Y. Prevalence and chracteristics of chronic muscloskeletal pain in Japan: A second survery of people with or without chronic pain. J Orthop Sci. 19: 339-350, 2014 Mar. (1.008)
Sumitani M, Yasunaga H, Uchida K, Horiguchi H, Nakamura M, Ohe K, Fushima K, Matsuda S, Yamada Y. Perioperative factors affecting the occurrence of acute complex regional pain syndrome following limb bone fracture surgery: Data from the Japanese Diagnosis Procedure Combination database. Rheumatology. 53: 1186-1193, 2014 Jul. (4.435)
Nagoshi N, Iwanami A, Toyama Y, Nakamura M. Factors contributing to improvement of syringomyelia after foramen magnum decompression for Chiari type I malNakamura M, Nishiwaki Y, Ushida T, Toyama Y. Prevalence and characteristics of chronic musculoskeletal pain in Japan: a second survey of people with or without chronic pain. J Orthop Sci. 19: 339-350, 2014 Mar. (1.008)formation. J Orthop Sci. 19: 418-423, 2014 May. (1.008)
Nakamura M, Nishiwaki Y, Ushida T, Toyama Y. Prevalence and characteristics of chronic musculoskeletal pain in Japan: a second survey of people with or without chronic pain. J Orthop Sci. 19: 339-350, 2014 Mar. (1.008)
Nakamura M, Nishiwaki Y, Sumitani M, Ushida T, Yamashita T, Konno S, Taguchi T, Toyama Y. Investigation of chronic musculoskeletal pain (third report): with special reference to the importance of neuropathic pain and psychogenic pain. J Orthop Sci. 19: 667-675, 2014 Jul. (1.008)
Nishimura S, Sasaki T, Shimizu A, Yoshida K, Iwai H, Koya I, Kobayashi Y, Itakura G, Shibata S, Ebise H, Horiuchi K, Kudoh J, Toyama Y, Anderson AJ, Okano H, Nakamura M. Global gene expression analysis following spinal cord injury in non-human primates. Exp Neurol. 261: 171-179, 2014 Nov. (4.617)
Shirasawa H, Ishii K, Iwanami A, Mikami S, Toyama Y, Matsumoto M, Nakamura M. Pediatric myxopapillary ependymoma treated with subtotal resection and radiation therapy: a case report and review of the literature. Spinal Cord. 52 Suppl 2: S18-20, 2014 Aug. (1.699)
Kondo T, Funayama M, Tsukita K, Hotta A, Yasuda A, Nori S, Kaneko S, Nakamura M, Takahashi R, Okano H, Yamanaka S, Inoue H. Focal transplantation of human iPSC-derived glial-rich neural progenitors improves lifespan of ALS mice. Stem Cell Reports. 12: 242-249, 2014 Aug.
Wu Z, Iwanami A, Yasuda A, Mikami S, Toyama Y, Nakamura M. Intramedullary cervicothoracic subependymoma: report of three cases and review of the literature. J Orthop Sci. epub, 2014 May. (1.008)
Sumitani M, Kogure T, Nakamura M, Shibata M, Yozu A, Otake Y, Yamada Y. Classification of the pain nature of CRPS type 1, based on patient complaints, into neuropathic pain and nociceptive/inflammatory pain, using the McGill Pain Questionnaire. J Anesthesia. in press 2014. (1.117)
Iwai H, Nori S, Nishimura S, Yasuda A, Takano O, Fujiyoshi K, Toyama Y, Okano H, Nakamura M. Transplantation of neural stem/progenitor cells at different locations in mice with spinal cord injury. Cell Transplant. 23, 11: 1451-1464, 2014. (3.570)
Okada E, Nakamura M, Koshida Y, Mukai K, Toyama Y, Matsumoto M. Breast carcinoma metastasis to meningioma in the thoracic spine: A case report and review of the literature. J Spinal Cord Med. epub, 2014 Mar. (1.878)
Tashiro S, Shinozaki M, Mukaino M, Renault-Mihara F, Toyama Y, Liu M, Nakamura M, Okano H. BDNF Induced by Treadmill Training Contributes to theSuppression of Spasticity and Allodynia After Spinal Cord Injury via Upregulationof KCC2. Neurorehabil Neural Repair. epub, 2014 Dec. (4.617)
Nagoshi N, Suda K, Morita T, Matsumoto S, Iimoto S, Yasui K, Komatsu M, Kobayashi Y, Minami A, Toyama Y, Matsumoto M, Nakamura M. C1 posterior arch screw as an auxiliary anchor in posterior reconstruction for atlantoaxial dislocation associated with type II odontoid fracture: a case report and review of the literature. Springerplus. Epub, 2014 Nov.
Itakura G, Kobayashi Y, Nishimura S, Iwai H, Takano M, Iwanami A, Toyama Y, Okano H, Nakamura M. Control of the survival and growth of human glioblastoma grafted into the spinal cord of mice by taking advantage of immunorejection. Cell transplantation. epub, 2014 May. (3.570)
Nakamura M, Ushida T, Toyama Y. Reply to letter to the editor by Toda. J Orthop Sci. epub, 2014 Nov. (1.008)
Nishikawa R, Hotta R, Shimojima N, Shibata S, Nagoshi N, Nakamura M, Matsuzaki Y, Okano HJ, Kuroda T, Okano H, Morikawa Y. Migration and differentiation of transplanted enteric neural crest-derived cells in murine model of Hirschsprung's disease. Cytotechnology. epub, 2014 Sep. (1.449)
Iwanami A, Kobayashi Y, Takano M, Mikami S, Toyama Y, Nakamura M. Invasive dumbbell spinal meningiomas: report of four cases and a review of the literature. J Orthop Sci. epub, 2014 Sep. (1.008)
Kobayashi Y, Iwanami A, Tsuji O, Takano M, Kimura T, Toyama Y, Nakamura M. Extramedullary non-myxopapillary ependymoma of the cauda equina; a case report and review of the literature. J Spine & Neurosurg. in press 2014.
Itakura G, Kobayashi Y, Nishimura S, Iwai H, Takano M, Iwanami A, Toyama Y, Okano H, Nakamura M. Controlling immune rejection is a fail-safe system against potential tumorigenicity after human iPSC-derived neural stem cell transplantation. PLoS One. in press 2014. (3.534)
Nori S, Okada Y, Nishimura S, Sasaki T, Itakura G, Kobayashi Y, Renault-Mihara F, Shimizu A, Koya I, Yoshida R, Kudoh J, Koike M, Uchiyama Y, Ikeda E, Toyama Y, Nakamura M, Okano H. Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model: oncogenic transformation with epithelial- mesenchymal transition. Stem Cell Reports. in press 2014.
Matsui T, Akamatsu W, Nakamura M, Okano H. Regeneration of the damaged central nervous system through reprogramming technology: basic concepts and potential application for cell replacement therapy. Exp Neurol. 260: 12-18, 2014 Oct. (4.617)
Iwanami A, Cloughesy TF, Cavenee WK, Mischel PS. Arsenic reverses glioblastoma resistance to mTOR-targeted therapies. Cell Cycle. 12, 10, 1473-4, 2013 May 15. (5.359)
Iwanami A, Gini B, Zanca C, Matsutani T, Assuncao A, Nael A, Dang J, Yang H, Zhu S, Kohyama J, Kitabayashi I, Cavenee WK, Cloughesy TF, Furnari FB, Nakamura M, Toyama Y, Okano H, and Mischel PS. PML mediates glioblastoma resistance to mammalian target of rapamycin (mTOR)-targeted therapies. Proc Natl Acad Sci U S A, epub, 2013 Feb 25. (9.681)
Okano H, Nakamura M, Yoshida K, Okada Y, Tsuji O, Nori S, Ikeda E, Yamanaka S, Miura K. Steps toward safe cell therapy using induced pluripotent stem cells. Circ Res. 112, 3, 523-33, 2013 Feb 1. (9.498)
Imai S, Ikegami D, Yamashita A, Shimizu T, Narita M, Niikura K, Furuya M, Kobayashi Y, Miyashita K, Okutsu D, Kato A, Nakamura A, Araki A, Omi K, Nakamura M, James Okano H, Okano H, Ando T, Takeshima H, Ushijima T, Kuzumaki N, Suzuki T, Narita M. Epigenetic transcriptional activation of monocyte chemotactic protein 3 contributes to long-lasting neuropathic pain. Brain. epub, 2013 Jan 30. (9.457)
Nakamura M, Okano H. Cell transplantation therapies for spinal cord injury focusing on induced pluripotent stem cells. Cell Res. 23, 1, 70-80, 2013 Jan. (8.190 )
Nishimura S, Yasuda A, Iwai H, Takano M, Kobayashi Y, Nori S, Tsuji O, Fujiyoshi K, Ebise H, Toyama Y, Okano H, Nakamura M. Time-dependent changes in the microenvironment of injured spinal cord affects the therapeutic potential of neural stem cell transplantation for spinal cord injury. Mol Brain. 8, 6:3, 2013 Jan. (4.202)
Guerrero AR, Uchida K, Nakajima H, Watanabe S, Nakamura M, Johnson WE, Baba H. Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice. J Neuroinflammation. 9, 40, 2012 Feb . (5.785)
Matsui T, Takano M, Yoshida K, Ono S, Fujisaki C, Matsuzaki Y, Toyama Y, Nakamura M, Okano H, Akamatsu W. Neural stem cells directly differentiated from partially reprogrammed fibroblasts rapidly acquire gliogenic competency. Stem Cells. 30, 6, 1109-19, 2012 Jun. (7.871)
Hara-Miyauchi C, Tsuji O, Hanyu A, Okada S, Yasuda A, Fukano T, Akazawa C, Nakamura M, Imamura T, Matsuzaki Y, Okano HJ, Miyawaki A, Okano H. Bioluminescent system for dynamic imaging of cell and animal behavior. Biochem Biophys Res Commun. 419, 2, 188-93, 2012 Mar. (2.595)
Nishikawa R, Shimojima N, Shibata S, Hotta R, Nagoshi N, Nakamura M, Matsuzaki Y, Okano H, Okano H, Morikawa Y. Migration and differentiation of transplanted neural crest stem/progenitor cells in murine model of hirschsprung's disease. Journal of Pediatric Surgery. epub, 2012. (1.308)
Nakamura M, Tsuji O, Nori S, Toyama Y, Okano H. Cell transplantation for spinal cord injury focusing on iPSCs. Expert Opin Biol Ther. 12, 7, 811-21, 2012 Jul. (3.279)
Konomi T, Fujiyoshi K, Hikishima K, Komaki Y, Tsuji O, Okano HJ, Toyama Y, Okano H, Nakamura M. Conditions for quantitative evaluation of injured spinal cord by in vivo diffusion tensor imaging and tractography: Preclinical longitudinal study in common marmosets. Neuroimage. 63, 4, 1841-53, 2012 Dec. (5.895)
Fujiyoshi K, Konomi T, Yamada M, Hikishima K, Tsuji O, Komaki Y, Momoshima S, Toyama Y, Nakamura M, Okano H. Diffusion tensor imaging and tractography of the spinal cord: From experimental studies to clinical application. Exp Neurol. epub, 2012 Jul 31. (4.699)
Takano M, Hikishima K, Fujiyoshi K, Shibata S, Yasuda A, Konomi T, Hayashi A, Baba H, Honke K, Toyama Y, Okano H, Nakamura M. MRI characterization of paranodal junction failure and related spinal cord changes in mice. PLoS One. 7, 12, e52904, 2012. (4.411)
Takano M, Komaki Y, Hikishima K, Konomi T, Fujiyoshi K, Tsuji O, Toyama Y, Okano H, Nakamura M. In vivo tracing of neural tracts in tiptoe walking yoshimura mice by diffusion tensor tractography. Spine (Phila Pa 1976). 38, 2, E66-72, 2013 Jan 15. (2.078)