Analysis for circulating endothelial progenitor cells in moyamoya disease

• Project/Area Number: 24390336
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Hokkaido University
• Principal Investigator: HOUKIN Kiyohiro 北海道大学, 大学病院, 教授 (90229146)
• Co-Investigator(Kenkyū-buntansha): KURODA Satoshi 富山大学, 大学院医学薬学研究部, 教授 (10301904) ; SHICHINOHE Hideo 北海道大学, 大学病院, 助教 (80374479)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2014: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2012: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
• Keywords: もやもや病 / 血管内皮前駆細胞 / iPS細胞 / サイトカイン

Outline of Final Research Achievements

1) Consumption of circulating EPC in MMD patients: Thirty-three patients with MMD and 14 healthy volunteers were registered to obtain mononuclear cells and plasma. In the patients, the circulating EPC was lower than control, and the circulating CD133+/CD34+ cells decreased after the operation, significantly. The level of bFGF was significantly lower in adult patients. The results suggested that EPCs would be consumed aggressively at the lesion. The pathological significance of bFGF in adult patients is still unclear.
2) Analysis of iPS cells from MMD patients: The iPS cell lines were established from PBMNCs of 3 MMD patients and 3 healthy persons. The endothelial differentiation was conducted on matrigel layer. The endothelial cells from MMD were impaired for the angiogenesis in vitro, significantly. In microarray analysis, it was found that KEGG pathway analysis of genes downregulated in MMD, that is, extracellular matrix receptor-related genes were significantly downregulated in MMD.

Research Products

• [Journal Article] Therapeutic Effects of Human Multilineage-Differentiating Stress Enduring (MUSE) Cell Transplantation into Infarct Brain of Mice. (2015)
  • Author(s): Yamauchi T, Kuroda Y, Morita T, Shichinohe H, Houkin K, Dezawa M, Kuroda S.
  • Journal Title: PLoS One. Volume: 10(3)
  • DOI: 10.1371/journal.pone.0116009
  • Peer Reviewed / Open Access
• [Journal Article] Neuroprotective effects of cilostazol are mediated by multiple mechanisms in a mouse model of permanent focal ischemia. (2015)
  • Author(s): Shichinohe H, Tan C, Abumiya T, Nakayama N, Kazumata K, Hokari M, Houkin K, Kuroda S.
  • Journal Title: Brain Res Volume: 1602 Pages: 53-61
  • DOI: 10.1016/j.brainres.2015.01.022
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chronic ischemia alters brain microstructural integrity and cognitive performance in adult moyamoya disease. (2015)
  • Author(s): Kazumata K, Tha KK, Narita H, Kusumi I, Shichinohe H, Ito M, Nakayama N, Houkin K.
  • Journal Title: Stroke Volume: 46(2) Pages: 354-360
  • DOI: 10.1161/strokeaha.114.007407
  • Peer Reviewed
• [Journal Article] Bone marrow stromal cells rescue ischemic brain by trophic effects and phenotypic change toward neural cells. (2015)
  • Author(s): Shichinohe H, Ishihara T, Takahashi K, Tanaka Y, Miyamoto M, Yamauchi T, Saito H, Takemoto H, Houkin K, Kuroda S.
  • Journal Title: Neurorehab Neural Repair Volume: 29(1) Pages: 80-89
  • DOI: 10.1177/1545968314525856
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Short-, middle- and long-term safety of superparamagnetic iron oxide-labeled allogeneic bone marrow stromal cell transplantation in rat model of lacunar infarction. (2014)
  • Author(s): Tan C, Shichinohe H, Abumiya T, Nakayama N, Kazumata K, Hokari M, Hamauchi S, Houkin K.
  • Journal Title: Neuropathology Volume: Epub ahead of print
  • DOI: 10.1111/neup.12180
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Platelet lysate and granulocyte-colony stimulating factor serve safe and accelerated expansion of human bone marrow stromal cells for stroke therapy. (2014)
  • Author(s): Yamauchi T, Saito H, Ito M, Shichinohe H, Houkin K, Kuroda S.
  • Journal Title: Transl Stroke Res Volume: 5(6) Pages: 701-710
  • DOI: 10.1007/s12975-014-0360-z
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Application of cell sheet technology to bone marrow stromal cell transplantation for rat brain infarct. (2014)
  • Author(s): Ito M, Shichinohe H, Houkin K, Kuroda S.
  • Journal Title: J Tissue Engineer Regen Med Volume: Epub ahead of print
  • DOI: 10.1002/term.1920
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Spatial Relationship between Cerebral Microbleeds, Moyamoya Vessels, and Hematoma in Moyamoya Disease. (2014)
  • Author(s): Kazumata K, Shinbo D, Ito M, Shichinohe H, Kuroda S, Nakayama N, Houkin K.
  • Journal Title: Journal of Stroke and CerebroVascular Diseases Volume: Epub ahead of print Pages: 1421-1428
  • DOI: 10.1016/j.jstrokecerebrovasdis.2013.12.007
  • Peer Reviewed
• [Journal Article] Bone Marrow Stromal Cells Rescue Ischemic Brain by Trophic Effects and Phenotypic Change Toward Neural Cells. (2014)
  • Author(s): Shichinohe H, Ishihara T, Takahashi K, Tanaka Y, Miyamoto M, Yamauchi T, Saito H, Takemoto H, Houkin K, Kuroda S.
  • Journal Title: Neurorehabil Neural Repair. Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] The frequency of postoperative stroke in moyamoya disease following combined revascularization: a single-university series and systematic review. (2014)
  • Author(s): Kazumata K, Ito M, Tokairin K, Ito Y, Houkin K, Nakayama N, Kuroda S, Ishikawa T, Kamiyama H.
  • Journal Title: J Neurosurg Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Bone marrow stromal cell transplantation enhances recovery of motor function after lacunar stroke in rats. (2013)
  • Author(s): Shichinohe H, Yamauchi T, Saito H, Houkin K, Kuroda S.
  • Journal Title: Acta Neurobiol Exp (Wars). Volume: 73(3) Pages: 354-363
  • Peer Reviewed
• [Journal Article] Ivy sign, misery perfusion, and asymptomatic moyamoya disease: FLAIR imaging and (15)O-gas positron emission tomography. (2013)
  • Author(s): Vuignier S, Ito M, Kurisu K, Kazumata K, Nakayama N, Shichinohe H, Shiga T, Kiss JZ, Tamaki N, Houkin K.
  • Journal Title: Acta Neurochir (Wien). Volume: 155(11) Pages: 2097-2104
  • DOI: 10.1007/s00701-013-1860-4
  • Peer Reviewed
• [Journal Article] 123I-iomazenil single photon emission computed tomography visualizes recovery of neuronal integrity by bone marrow stromal cell therapy in rat infarct brain. (2013)
  • Author(s): Saito H, Magota K, Zhao S, Kubo N, Kuge Y, Shichinohe H, Houkin K, Tamaki N, Kuroda S.
  • Journal Title: Stroke Volume: 44(10) Pages: 2869-2874
  • DOI: 10.1161/strokeaha.113.001612
  • Peer Reviewed
• [Journal Article] Incidence, locations, and longitudinal course of silent microbleeds in movamova disease : a Drospective T2*-weighted MRI study. (2013)
  • Author(s): Kuroda S, Kashiwazaki D, Ishikawa T, Nakavama N, Houkin K
  • Journal Title: Stroke Volume: 44(2) Pages: 516-518
  • DOI: 10.1161/strokeaha.112.678805
  • Peer Reviewed
• [Journal Article] Effective Surgical Revascularization Improves Cerebral Hemodynamics and Resolves Headache in Pediatric Moyamoya Disease (2012)
  • Author(s): Kawabori M, Kuroda S, Nakayama N, Hirata K, Shiga T, Houkin K, Tamaki N.
  • Journal Title: World Neurosurg. Volume: (e-pub)
  • DOI: 10.1016/j.wneu.2012.08.005
  • NAID: 120006482586
  • Peer Reviewed
• [Journal Article] Predictors and Clinical Features of Postoperative Hyperperfusion after Surgical Revascularization for Moyamoya Disease : A Serial Single Photon Emission CT/Positron Emission Tomography Study. (2012)
  • Author(s): Uchino H, Kuroda S, Hirata K, Shiga T, Houkin K, Tamaki N.
  • Journal Title: Stroke Volume: 43(10) Pages: 2610-2616
  • DOI: 10.1161/strokeaha.112.654723
  • NAID: 10031131119
  • Peer Reviewed
• [Journal Article] Transient Crossed Cerebellar Diaschisis Due to Cerebral Hyperperfusion Following Surgical Revascularization for Moyamoya Disease (2012)
  • Author(s): Hokari M, Kuroda S, Simoda Y, Uchino H, Hirata K, Shiga T, Nakayama N, Houkin K, Tamaki N.
  • Journal Title: Neurol. Med. Chir.(Tokyo) Volume: 52(5) Issue: 5 Pages: 350-353
  • DOI: 10.2176/nmc.52.350
  • NAID: 10030314688
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed
• [Journal Article] Bypass Surgery for Moyamoya Disease (2012)
  • Author(s): Kuroda S, Houkin K.
  • Journal Title: Neurol. Med. Chir.(Tokyo) Volume: 52(5) Issue: 5 Pages: 287-294
  • DOI: 10.2176/nmc.52.287
  • NAID: 10030314424
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed
• [Presentation] Analysis for the role of angiogenic factors on endothelial cells derived from moyamoya disease-iPSCs (2015)
  • Author(s): Hamauchi S, Shichinohe H, Houkin K et al.
  • Organizer: 4th International Moyamoya Meeting
  • Place of Presentation: Kaiserin-Friedrich-Haus（Berlin, Germany）
  • Year and Date: 2015-07-02 – 2015-07-04
• [Presentation] もやもや病iPS細胞由来血管内皮細胞におけるangiogenic factorへの反応性の解析 (2015)
  • Author(s): 浜内祝嗣、七戸秀夫、伊東雅基、長内俊也、穂刈正昭、中山若樹、数又研、江良択実、寳金清博
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2015-03-19 – 2015-03-21
• [Presentation] 123I-iomazenil single photon emission computed tomography visualizes recovery of neuronal integrity by bone marrow stromal cell therapy in rat infarct brain. (2013)
  • Author(s): Saito H, Magota K, Zhao S, Kubo N, Kuge Y, Shichinohe H, Houkin K, Tamaki N, Kuroda S
  • Organizer: WFNS XV World Congress of Neurosurgery
  • Place of Presentation: COEX Convention Center (Seoul, South Korea)
• [Remarks] Hokkaido University Moyamoya Center
  • URL: http://moyamoya.neurosurgery-hokudai.jp
• [Remarks] 北海道大学 大学院医学研究科・医学部 脳神経外科
  • URL: http://www.neurosurgery-hokudai.jp