Donor-host interaction of engrafted neural stem progenitor cells in injured spinal cord

• Project/Area Number: 25713053
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kyushu University
• Principal Investigator: Okada Seiji 九州大学, 医学(系)研究科(研究院), 准教授 (30448435)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000); Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2014: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2013: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: 脊髄損傷 / 神経幹細胞 / 慢性期

Outline of Final Research Achievements

The transplantation of neural stem/precursor cells (NSPCs) is a promising therapeutic strategy for spinal cord injury (SCI) , however, few studies have investigated NSPC transplantation for the severe injury nor chronic phase of SCI, and its therapeutic efficacy remains controversial. In this study, we demonstrated that the interactive synaptic reorganization between engrafted NSPCs and spared host neurons is crucial for functional recovery. In addition, even with the adequate capacity in generating neurons/oligodendrocytes and producing therapeutic molecules, engrafted NSPCs did not improve locomotor function, indicating that failure in chronic transplantation is not due to the lack of therapeutic activities of engrafted NSPCs but the refractory state of chronically injured spinal cords. Environmental modulation, rather modification of transplanting cells, will be significant for successful translation of stem cell-based therapies for SCI.

Research Products

• [Journal Article] Risk factors for adjacent segment pathology requiring additional surgery after single-level spinal fusion: impact of pre-existing spinal stenosis demonstrated by preoperative myelography. (2016)
  • Author(s): Yugué I, Okada S, Masuda M, Ueta T, Maeda T, Shiba K.
  • Journal Title: Eur Spine Journal Volume: 25 Issue: 5 Pages: 1542-1549
  • DOI: 10.1007/s00586-015-4185-6
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Position of the Aorta Relative to the Vertebrae in Patients With Lenke Type 1 Adolescent Idiopathic Scoliosis. (2016)
  • Author(s): Bekki H, Harimaya K, Matsumoto Y, Hayashida M, Okada S, Doi T, Iwamoto Y.
  • Journal Title: Spine Volume: 41 Issue: 7 Pages: 585-590
  • DOI: 10.1097/brs.0000000000001257
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury. (2015)
  • Author(s): Yokota K, Kobayakawa K, Kubota K, Miyawaki A, Okano H, Ohkawa Y, Iwamoto Y, Okada S.
  • Journal Title: Stem Cell Reports. Volume: 5 Issue: 2 Pages: 264-277
  • DOI: 10.1016/j.stemcr.2015.06.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Scoliosis in patients with multiple hereditary exostoses. (2015)
  • Author(s): Matsumoto Y, Matsumoto K, Harimaya K, Okada S, Doi T, Iwamoto Y.
  • Journal Title: Eur Spine Journal Volume: 24 Issue: 7 Pages: 1568-1573
  • DOI: 10.1007/s00586-015-3883-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone. (2015)
  • Author(s): Hatano M, Matsumoto Y, Fukushi J, Matsunobu T, Endo M, Okada S, Iura K, Kamura S, Fujiwara T, Iida K, Fujiwara Y, Nabeshima A, Yokoyama N, Fukushima S, Oda Y, Iwamoto Y.
  • Journal Title: Clin Exp Metastasis. Volume: 32 Issue: 6 Pages: 579-591
  • DOI: 10.1007/s10585-015-9729-y
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Spatial re-organization of myogenic regulatory sequences temporally controls gene expression (2015)
  • Author(s): Harada A, Mallappa C, Okada S, Butler JT, Baker SP, Lawrence JB, Ohkawa Y, Imbalzano AN.
  • Journal Title: Nucleic Acids Research Volume: 43 Issue: 4 Pages: 2008-2021
  • DOI: 10.1093/nar/gkv046
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans (2014)
  • Author(s): Kobayakawa K, Kumamaru H, Saiwai H, Kubota K, Ohkawa Y, Kishimoto J, Yokota K, Ideta R, Shiba K, Tozaki-Saitoh H, Inoue K, Iwamoto Y, Okada S
  • Journal Title: Science Translational Medicine Volume: 6 Issue: 256 Pages: 256-256
  • DOI: 10.1126/scitranslmed.3009430
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sequential changes of ascending myelopathy after spinal cord injury on MRI. (2014)
  • Author(s): Okada S*, Saito T, Kawano O, Hayashida M, Matsumoto Y, Harimaya K, Iwamoto Y.
  • Journal Title: Spine Journal. Volume: 14 Issue: 12 Pages: e9-e14
  • DOI: 10.1016/j.spinee.2014.08.449
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A shallow chest correlates with the aortic position in the normal spine:features resembling those observed in structural scoliosis. (2014)
  • Author(s): Doi T, Masumoto Y, Tono O, Tarudado K, Harimaya K, Okada S, Kubota K, Hayashida M, Iwamoto Y.
  • Journal Title: Scoliosis. Volume: 9 Issue: 1 Pages: 14-18
  • DOI: 10.1186/1748-7161-9-14
  • Peer Reviewed
• [Journal Article] Instability of the vertebrae remains following balloon kyphoplasty. (2014)
  • Author(s): Tarukado K, Tono O, Ikuta K, Harimaya K, Matsumoto Y, Okada S, Hayashida M, Iwamoto Y, Doi T.
  • Journal Title: Global Spine Journal. Volume: 4 Issue: 2 Pages: 89-92
  • DOI: 10.1055/s-0034-1370790
  • Peer Reviewed
• [Journal Article] Production of a Monoclonal Antibody for C/EBPB : The Subnuclear Localization of C/EBPB in Mouse L929 Cells. (2014)
  • Author(s): Harada A, Okazaki E, Okada S, Tachibana T, Ohkawa Y.
  • Journal Title: Monoclonal Antibodies Immunodiagnosis and Immunotherapy Volume: 33 Issue: 1 Pages: 34-37
  • DOI: 10.1089/mab.2013.0069
  • Peer Reviewed
• [Journal Article] The therapeutic activities of engrafted neural stem/precursor cells are not dormant in the chronically injured spinal cord (2013)
  • Author(s): Kumamaru H, Kobayakawa K, Saiwai H, Kubota K, Yokota K, Ohkawa Y, Shiba K, Iwamoto Y, Okada S
  • Journal Title: Stem Cells Volume: 31(8) Issue: 8 Pages: 1535-47
  • DOI: 10.1002/stem.1404
  • Peer Reviewed
• [Journal Article] Ly6C+ Ly6G- Myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury. (2013)
  • Author(s): Saiwai H, Kumamaru H, Ohkawa Y, Kubota K, Kobayakawa K, Yamada H, Yokomizo T, Iwamoto Y, Okada S.
  • Journal Title: J Neurochem. Volume: 125 Issue: 1 Pages: 74-88
  • DOI: 10.1111/jnc.12135
  • Peer Reviewed
• [Journal Article] Disturbance of ribcage development causes progressive thoracic scoliosis: The creation of a nonsurgical structural scoliosis model in mice. (2013)
  • Author(s): Kubota K, Doi T, Murata M, Kobayakawa K, Matsumoto Y, Harimaya K, Shiba K, Hashizume M, Iwamoto Y, Okada S.
  • Journal Title: J Bone Joint Surg. Volume: 95 Issue: 18 Pages: e130-e130
  • DOI: 10.2106/jbjs.l.01381
  • Peer Reviewed
• [Journal Article] Clinical relationship between cervical spinal canal stenosis and traumatic cervical spinal cord injury without major fracture or dislocation. (2013)
  • Author(s): Takao T, Morishita Y, Okada S, Maeda T, Katoh F, Ueta T, Mori E, Yugeu I, Kawano O, Shiba K.
  • Journal Title: Eur Spine J. Volume: 22 Issue: 10 Pages: 2228-2231
  • DOI: 10.1007/s00586-013-2865-7
  • Peer Reviewed
• [Presentation] 基礎研究による脊椎疾患の病態解明 (2015)
  • Author(s): 岡田誠司
  • Organizer: 第25回弘前大学整形外科夏の研修会
  • Place of Presentation: 弘前市
  • Year and Date: 2015-08-06
  • Invited
• [Presentation] 炎症は再生を抑制するかー脊髄損傷後の炎症と再生 (2015)
  • Author(s): 岡田誠司
  • Organizer: 第３６回日本炎症再生医学会
  • Place of Presentation: 東京都
  • Year and Date: 2015-07-21
  • Invited
• [Presentation] マウス発育性側弯症モデルの確立ー肋椎関節のインバランスは発育性側弯の発症要因となりうる (2015)
  • Author(s): 岡田誠司
  • Organizer: 第88回日本整形外科学会学術総会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-05-21
• [Presentation] 損傷脊髄環境と移植神経幹細胞の生着率 (2014)
  • Author(s): 岡田誠司
  • Organizer: 第29回日本整形外科学会基礎学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-09 – 2014-10-10
  • Invited
• [Presentation] 脊髄損傷後の急性期高血糖は運動機能回復を有意に阻害する (2014)
  • Author(s): 岡田誠司
  • Organizer: 第49回日本脊髄障害医学会
  • Place of Presentation: 旭川
  • Year and Date: 2014-09-11 – 2014-09-12
• [Presentation] Acute hyperglycemia exacerbates functional outcomes in human and mouse spinal cord injury via NF-kB pathway. (2014)
  • Author(s): Kobayakawa K, Saiwai H, Kumamaru H, Kubota K, Yokota Y, Ohkawa Y, Shiba K, Iwamoto Y, Okada S.
  • Organizer: Joint Congress of European Neurology
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2014-05-31 – 2014-06-03
• [Presentation] Limited efficacy of engrafted neural stem and progenitor cells for severe spinal cord injury. (2014)
  • Author(s): Yokota K, Okada S, Kobayakawa K, Saito T, Iwamoto Y.
  • Organizer: Joint Congress of European Neurology
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2014-05-31 – 2014-06-03
• [Presentation] 脊髄損傷後の急性期高血糖は運動機能回復を有意に阻害する (2014)
  • Author(s): 岡田誠司
  • Organizer: 第87回日本整形外科学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2014-05-23 – 2014-05-25
• [Presentation] 脊髄損傷に対する細胞移植治療研究の現状と展望 (2013)
  • Author(s): 岡田誠司
  • Organizer: 第35回九州理学療法士•作業療法士合同学会（学会基調講演）
  • Place of Presentation: 熊本市
  • Invited
• [Presentation] 脊髄損傷に対する治験―ステロイド大量療法の歴史から学ぶ (2013)
  • Author(s): 岡田誠司
  • Organizer: 第48回日本脊髄障害医学会
  • Place of Presentation: 福岡市
  • Invited
• [Presentation] 慢性期脊髄損傷に対する神経幹細胞移植 (2013)
  • Author(s): 岡田誠司
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 千葉市
  • Invited
• [Presentation] Hyperglycemia-induced microglial overactivation deteriorates the secondary injury via NF-κB pathway after spinal cord injury. (2013)
  • Author(s): Kobayakawa K, Saiwai H, Kumamaru H, Kubota K, Ohkawa Y, Shiba K, Yokota Y, Iwamoto Y, Okada S.
  • Organizer: The 43th Annual Meeting of Society for Neuroscience
  • Place of Presentation: San Diego
• [Presentation] Structural and functional changes of distal site to the lesion after chronic complete spinal cord injury. (2013)
  • Author(s): Yokota K, Kobayakawa K, Iwamoto Y, Okada S.
  • Organizer: The 43th Annual Meeting of Society for Neuroscience
  • Place of Presentation: San Diego