Shinozaki, Munehisa

写真a

Affiliation

School of Medicine, Department of Physiology (Shinanomachi)

Position

Project Senior Assistant Professor (Non-tenured)/Project Assistant Professor (Non-tenured)/Project Lecturer (Non-tenured)

 

Research Areas 【 Display / hide

  • General physiology

Research Keywords 【 Display / hide

  • regeneration

 

Papers 【 Display / hide

  • Concise Review: Laying the Groundwork for a First-In-Human Study of an Induced Pluripotent Stem Cell-Based Intervention for Spinal Cord Injury

    Tsuji O., Sugai K., Yamaguchi R., Tashiro S., Nagoshi N., Kohyama J., Iida T., Ohkubo T., Itakura G., Isoda M., Shinozaki M., Fujiyoshi K., Kanemura Y., Yamanaka S., Nakamura M., Okano H.

    Stem Cells (Stem Cells)  37 ( 1 ) 6 - 13 2019.01

    ISSN  10665099

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    © 2018 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press There have been numerous attempts to develop stem cell transplantation approaches to promote the regeneration of spinal cord injury (SCI). Our multicenter team is currently planning to launch a first-in-human clinical study of an induced pluripotent stem cell (iPSC)-based cell transplant intervention for subacute SCI. This trial was conducted as class I regenerative medicine protocol as provided for under Japan's Act on the Safety of Regenerative Medicine, using neural stem/progenitor cells derived from a clinical-grade, integration-free human “iPSC stock” generated by the Kyoto University Center for iPS Cell Research and Application. In the present article, we describe how we are preparing to initiate this clinical study, including addressing the issues of safety and tumorigenesis as well as practical problems that must be overcome to enable the development of therapeutic interventions for patients with chronic SCI. Stem Cells 2019;37:6–13.

  • Treatment with a Gamma-Secretase Inhibitor Promotes Functional Recovery in Human iPSC- Derived Transplants for Chronic Spinal Cord Injury

    Okubo T., Nagoshi N., Kohyama J., Tsuji O., Shinozaki M., Shibata S., Kase Y., Matsumoto M., Nakamura M., Okano H.

    Stem Cell Reports (Stem Cell Reports)  11 ( 6 ) 1416 - 1432 2018.12

    ISSN  22136711

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    © 2018 The Authors In this article, Okano and colleagues show that the GSI-treated hiPSC-NS/PCs caused significantly enhanced axonal regrowth, remyelination, inhibitory synapse formation with the host neural circuitry, and reticulo spinal tract fiber formation. These favorable outcomes contributed to motor function improvement. Therefore, treating cells with GSI provides a beneficial effect after transplantation, even in the chronic phase following SCI.

  • Assessing cortical plasticity after spinal cord injury by using resting-state functional magnetic resonance imaging in awake adult mice

    Matsubayashi K., Nagoshi N., Komaki Y., Kojima K., Shinozaki M., Tsuji O., Iwanami A., Ishihara R., Takata N., Matsumoto M., Mimura M., Okano H., Nakamura M.

    Scientific Reports (Scientific Reports)  8 ( 1 )  2018.12

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    © 2018, The Author(s). Neural connectivity has recently been shown to be altered after spinal cord injury (SCI) not only in the spinal cord but also in the brain. However, to date, no studies have analyzed the functional alterations after SCI in various areas of the cerebral cortex over time. To examine the plasticity of the neural connectivity in the brain after SCI, we performed resting-state functional magnetic resonance imaging (rs-fMRI) in awake adult mice pre- and post-SCI. After a complete thoracic SCI, the functional connectivity between the primary motor (MOp) and primary sensory (SSp) areas was significantly decreased during the chronic phase. In contrast, the connectivity between the MOp and motivation area was increased. Thus, impairments in sensory and motor connections after SCI led to a time-dependent compensatory upregulation of “motor functional motivation”. Moreover, the functional connectivity between the SSp and pain-related areas, such as the caudoputamen (CP) and the anterior cingulate area (ACA), was strengthened during the chronic phase, thus suggesting that rs-fMRI can indicate the presence of neuropathic pain after SCI. Therefore, rs-fMRI is a useful tool for revealing the pathological changes that occur in the brain after SCI.

  • The Amelioration of Pain-Related Behavior in Mice with Chronic Spinal Cord Injury Treated with Neural Stem/Progenitor Cell Transplantation Combined with Treadmill Training

    Tashiro S., Nishimura S., Shinozaki M., Takano M., Konomi T., Tsuji O., Nagoshi N., Toyama Y., Liu M., Okano H., Nakamura M.

    Journal of Neurotrauma (Journal of Neurotrauma)  35 ( 21 ) 2561 - 2571 2018.11

    ISSN  08977151

     View Summary

    © Copyright 2018, Mary Ann Liebert, Inc., publishers 2018. Progress in regenerative medicine is realizing the possibility of neural regeneration and functional recovery in spinal cord injury (SCI). Recently, rehabilitation has attracted much attention with respect to the synergistic promotion of functional recovery in combination with neural stem/progenitor cell (NS/PC) transplantation, even in the chronic refractory phase of SCI. Nevertheless, sensory disturbance is one of the most prominent sequelae, even though the effects of combination or single therapies have been investigated mostly in the context of motor recovery. To determine how combination therapy with treadmill training (TMT) and NS/PC transplantation affects the manifestation of thermal allodynia and tactile hyperalgesia in chronic phase SCI, four groups of SCI mice were used to assess pain-related behavior and histological changes: combined transplantation and TMT therapy, transplantation only, TMT only, and control groups. Thermal allodynia and coarse touch-pressure hyperalgesia exhibited significant recovery in the combined therapy group in comparison with controls, whereas there were no significant differences with fine touch-pressure hyperalgesia and motor function. Further investigation revealed fewer fibers remaining in the posterior funiculus, which contained the tracts associated with the two modalities showing less recovery; that is, touch-pressure hyperalgesia and motor function. A significant correlation was only observed between these two modalities. Although no remarkable histological recovery was found within the lesion epicenter, changes indicating amelioration of pain were observed in the lumbar enlargement of the combination therapy group. Our results suggest that amelioration of thermal allodynia and tactile hyperalgesia can be brought about by the additive effect of NS/PC transplantation and TMT. The degree of recovery seems dependent on the distribution of damage.

  • LOTUS Inhibits Neuronal Apoptosis and Promotes Tract Regeneration in Contusive Spinal Cord Injury Model Mice

    Ito S., Nagoshi N., Tsuji O., Shibata S., Shinozaki M., Kawabata S., Kojima K., Yasutake K., Hirokawa T., Matsumoto M., Takei K., Nakamura M., Okano H.

    eNeuro (eNeuro)  5 ( 5 )  2018.09

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    Nogo receptor-1 (NgR1) signaling is involved in the limitation of axonal regeneration following spinal cord injury (SCI) through collapsing the growth cone and inhibiting neurite outgrowth. Lateral olfactory tract usher substance (LOTUS), a NgR antagonist, suppresses these pathological conditions. A previous report demonstrated the positive effects of LOTUS expression on motor function through raphespinal tract regeneration using pan-neuronally LOTUS-overexpressing transgenic mice. However, this report used a hemi-section model, which does not represent the majority of clinical SCI cases, and lacked a detailed histological analysis of other descending tracts. To determine the true therapeutic effects of LOTUS, we used a more clinically relevant contusive SCI model in female transgenic mice. Definitive tracing analyses revealed that LOTUS promoted the extensive regeneration of the reticulospinal tract across the lesion site and suppressed axonal dieback of corticospinal tract (CST). A significant increase in raphespinal tract fibers was seen from the subacute to the chronic phase after the injury, strongly suggesting that LOTUS promoted translesional elongation of this tract. Furthermore, histological analyses revealed that LOTUS had a neuroprotective effect on the injured spinal cord through suppressing cellular apoptosis during the acute phase. These neuroprotective and regenerative effects contributed to significant motor functional recovery and restoration of the motor evoked potential (MEP). Therefore, LOTUS application could prove beneficial in the treatment of SCI by promoting axonal regeneration of some descending fibers, reducing axonal dieback of CST fibers and encouraging motor function recovery.

 

Courses Taught 【 Display / hide

  • PHYSIOLOGY 2

    2021

  • PHYSIOLOGY 2

    2020