Therapeutic benefits of the genetically-engineering mesenchymal stem cells for sub-acute cerebral ischemia

• Project/Area Number: 20390388
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Sapporo Medical University
• Principal Investigator: HONMOU Osamu 札幌医科大学, 医学部, 教授 (90285007)
• Co-Investigator(Kenkyū-buntansha): HAMADA Hirofumi 東京薬科大学, 生命科学部, 教授 (00189614) ; HOUKIN Kiyohiro 北海道大学, 大学院・医学研究科, 教授 (90229146)
• Project Period (FY): 2008 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2009: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: 移植・再生医療 / 再生医学 / 神経科学 / 脳・神経 / 発生・分化

Research Abstract

We have reported that transplantation of bone marrow stem cells has demonstrated therapeutic efficacy in animal models of acute cerebral ischemia. In the present study, we transplanted bone marrow stem cells into middle cerebral artery occlusion model rats to study their potential therapeutic benefit in the subacute phase. This work demonstrates that highly purified bone marrow stem cells are neuroprotective and angeigenetic in subacute cerebral ischemia models.

Research Products

• [Journal Article] Mesenchymal stem cells : therapeutic outlook for stroke (2012)
  • Author(s): Honmou O, Onodera R, Sasaki M, Waxman SG, Kocsis JD
  • Journal Title: Trends Mol Med Volume: 18 Pages: 292-297
  • Peer Reviewed
• [Journal Article] Expression of Aquaporin-4 Augments Cytotoxic Brain Edema after Traumatic Brain Injury during Acute Ethanol Exposure (2011)
  • Author(s): Katada R, Nishitani Y, Honmou O, Mizuo K, Okazaki S, Tateda K, et al Katada R, Nishitani Y, Honmou O, Mizuo K, Okazaki S, Tateda K, et al
  • Journal Title: Am J Pathol Volume: 180 Pages: 17-23
  • Peer Reviewed
• [Journal Article] Development of a middle cerebral artery occlusion model in the nonhuman primate and a safety study of I. v. Infusion of human mesenchymal stem cells (2011)
  • Author(s): Sasaki M, Honmou O, Radtke C, Kocsis JD
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] Identification of chemoattractive factors involved in the migration of bone marrow-derived mesenchymal stem cells to brain lesions caused by prion (2011)
  • Author(s): Song CH, Honmou O, Furuoka H, Horiuchi M
  • Journal Title: J Virol Volume: 85 Issue: 10 Pages: 11069-11078
  • DOI: 10.1371/journal.pone.0026577
  • NAID: 120004027230
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cells transmigrate across brain microvascular endothelial cell monolayers through transiently formed inter-endothelial gaps (2011)
  • Author(s): Matsushita T, Kibayashi T, Katayama T, Yamashita Y, Suzuki S, Kawamata J, Honmou O, Minami M, Shimohama S
  • Journal Title: Neurosci Lett Volume: 8 Pages: 41-5
  • Peer Reviewed
• [Journal Article] Intravenous administration of auto serum-expanded autologous mesenchymal stem cells into stroke (2011)
  • Author(s): Honmou O, Houkin K, Matsunaga T, Niitsu Y, Ishiai S, Onodera R, Waxman SG, Kocsis JD
  • Journal Title: Brain Volume: 134 Pages: 1790-1807
  • Peer Reviewed
• [Journal Article] Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke (2011)
  • Author(s): Honmou, O., et al
  • Journal Title: BRAIN Volume: 134 Issue: 6 Pages: 1790-1807
  • DOI: 10.1093/brain/awr063
  • Peer Reviewed
• [Journal Article] Identification of chemoattractive factors involved in the migration of bone marrow-derived mesenchymal stem cells to brain lesions caused by prion (2011)
  • Author(s): Song, C.H., et al
  • Journal Title: J.Virol. Volume: 85 Issue: 21 Pages: 11069-11078
  • DOI: 10.1128/jvi.05318-11
  • Peer Reviewed
• [Journal Article] Therapeutic time window of mesenchymal stem cells derived from bone marrow after cerebral ischemia (2010)
  • Author(s): Komatsu K, Honmou O, Suzuki J, Houkin K, Hamada H, Kocsis JD
  • Journal Title: Brain Res Volume: 1334 Pages: 84-92
  • Peer Reviewed
• [Journal Article] Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia (2010)
  • Author(s): Zheng W, Honmou O, Miyata K, Harada K, Suzuki J, Liu H, Houkin K, Hamada H, Kocsis JD
  • Journal Title: Brain Res Volume: 1310 Pages: 8-16
  • Peer Reviewed
• [Journal Article] Therapeutic time window of mesenchymal stem cells derived from bone marrow after cerebral ischemia. (2010)
  • Author(s): Komatsu K, Honmou O, Suzuki J, Houkin K, Hamada H, Kocsis JD
  • Journal Title: Brain Res 1334 Pages: 84-92
  • Peer Reviewed
• [Journal Article] Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia. (2010)
  • Author(s): Zheng W, Honmou O, Miyata K, Harada K, Suzuki J, Liu H, Houkin K, Hamada H, Kocsis JD
  • Journal Title: Brain Res 1310 Pages: 8-16
  • Peer Reviewed
• [Journal Article] Therapeutic time window of mesenchymal stem cells derived from bone marrow after cerebral ischemia. (2010)
  • Author(s): Komatsu, K., et al.
  • Journal Title: BRAIN RESEARCH Volume: 1343 Pages: 84-92
  • Peer Reviewed
• [Journal Article] Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia (2010)
  • Author(s): Zhen, et al
  • Journal Title: Brain Research 1310 Pages: 8-16
  • Peer Reviewed
• [Journal Article] Effect of transplantation of bone marrow-derived mesenchymal stem cells on mice infected with prions (2009)
  • Author(s): Song CH, Honmou O, Ohsawa N, Nakamura K, Hamada H, Furuoka H, Hasebe R, Horiuchi M
  • Journal Title: Journal of Virology Volume: 83 Pages: 5918-5927
  • NAID: 120001629752
  • Peer Reviewed
• [Journal Article] Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells after cerebral ischemia (2009)
  • Author(s): Toyama K, Honmou O, Harada K, Suzuki J, Houkin K, Hamada H, Kocsis JD
  • Journal Title: Exp Neurol Volume: 213 Pages: 47-55
  • Peer Reviewed
• [Journal Article] Effect of transplantation of bone marrow-derived mesenchymal stem cells on mice infected with prions. (2009)
  • Author(s): Song CH, Honmou O, Ohsawa N, Nakamura K, Hamada H, Furuoka H, Hasebe R, Horiuchi M
  • Journal Title: Journal of Virology 83 Pages: 5918-5927
  • NAID: 120001629752
  • Peer Reviewed
• [Journal Article] Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells after cerebral ischemia. (2009)
  • Author(s): Toyama K, Honmou O, Harada K, Suzuki J, Houkin K, Hamada H, Kocsis JD
  • Journal Title: Exp Neurol 216 Pages: 47-55
  • Peer Reviewed
• [Journal Article] Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells after cerebral ischemia (2009)
  • Author(s): Toyama, et al.
  • Journal Title: Experimental Neurology 216 Pages: 47-55
  • Peer Reviewed
• [Journal Article] Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats (2008)
  • Author(s): Omori Y, Honmou O, Harada K, Suzuki J, Houkin K, Kocsis JD
  • Journal Title: Brain Res Volume: 1236 Pages: 30-38
  • Peer Reviewed
• [Journal Article] Therapeutic benefits by human mesenchymal stem cells(hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia (2008)
  • Author(s): Onda T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD
  • Journal Title: J Cereb Blood Flow Metab Volume: 28 Pages: 329-340
  • Peer Reviewed
• [Journal Article] Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats. (2008)
  • Author(s): Omori Y, Honmou O, Harada K, Suzuki J, Houkin K, Kocsis JD
  • Journal Title: Brain Res 1236 Pages: 30-38
  • Peer Reviewed
• [Journal Article] Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia. (2008)
  • Author(s): Onda T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD
  • Journal Title: J Cereb Blood Flow Metab 28 Pages: 329-340
  • Peer Reviewed
• [Journal Article] Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats (2008)
  • Author(s): Omori, et al.
  • Journal Title: Brain Research 1236 Pages: 30-38
  • Peer Reviewed
• [Journal Article] Therapeutic benefits by Ang-1 gene-modified human mesenchymal stem cells after cerebral ischemia. (2008)
  • Author(s): Onda, et al.
  • Journal Title: Journal of Cerebral Blood Flow & Metabolism 28 Pages: 329-340
  • Peer Reviewed
• [Presentation] 脳梗塞の再生医療 (2011)
  • Author(s): 本望修
  • Organizer: 第18回日本血液代替物学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-10-28
• [Presentation] Intra venous transplantation of auto serum expanded autologous mesenchymal stem cells derived from bone marrow into stroke patients (2011)
  • Author(s): 本望修
  • Organizer: 第73回日本血液学会学術集
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] 脳卒中を治す細胞治療の現状と将来 (2011)
  • Author(s): 本望修
  • Organizer: 第20回日本脳ドック学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-08
• [Presentation] 脳卒中を治す～細胞治療の現状と将来～ (2011)
  • Author(s): 本望修
  • Organizer: 第20回日本脳ドック学会総会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2011-07-08
• [Presentation] 自己培養骨髄幹細胞による脳梗塞の再生医療 (2011)
  • Author(s): 本望修
  • Organizer: 第2回日本ニューロリハビリテーション学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-02-12
• [Presentation] 脳神経疾患に対する骨髄幹細胞移植による救急医療 (2011)
  • Author(s): 本望修
  • Organizer: 第16回日本脳神経外科救急学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-01-30
• [Presentation] 脳神経疾患に対する骨髄幹細胞移植による救急医療 (2011)
  • Author(s): 本望修
  • Organizer: 第16回 学術集会 日本脳神経外科救急学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-01-30
• [Presentation] 脊髄損傷に対する培養骨髄幹細胞の静脈内投与社団法人日本脳神経外科学会 (2010)
  • Author(s): 本望修
  • Organizer: 第69回学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-28
• [Presentation] 脊髄損傷に対する培養骨髄幹細胞の静脈内投与 (2010)
  • Author(s): 本望修
  • Organizer: 社団法人日本脳神経外科学会第69回学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-28
• [Presentation] 脊髄損傷に対する培養骨髄幹細胞の静脈内投与 (2010)
  • Author(s): 本望修
  • Organizer: 社団法人 日本脳神経外科学会 第69回 学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-28
• [Presentation] 脳梗塞の再生医療 (2010)
  • Author(s): 本望修
  • Organizer: 第13回日本栓子検出と治療学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-19
• [Presentation] 脳梗塞の再生医療 (2010)
  • Author(s): 本望修
  • Organizer: 第13回 日本栓子検出と治療学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-19
• [Presentation] 脳梗塞に対する自己骨髄幹細胞を用いた再生医療 (2010)
  • Author(s): 本望修
  • Organizer: 第19回日本意識障害学会
  • Place of Presentation: 山口
  • Year and Date: 2010-07-24
• [Presentation] 脳梗塞に対する自己骨髄幹細胞を用いた再生医療 (2010)
  • Author(s): 本望修
  • Organizer: 第19回 日本意識障害学会
  • Place of Presentation: 山口
  • Year and Date: 2010-07-24
• [Presentation] 脳梗塞に対する自己骨髄幹細胞の静脈内投与 (2010)
  • Author(s): 本望修
  • Organizer: 第13回日本病院脳神経外科学会
  • Place of Presentation: 釧路
  • Year and Date: 2010-07-17
• [Presentation] 脳梗塞に対する自己骨髄幹細胞の静脈内投与 (2010)
  • Author(s): 本望修
  • Organizer: 第13回 日本病院脳神経外科学会
  • Place of Presentation: 釧路
  • Year and Date: 2010-07-17
• [Presentation] 脳梗塞に対する自己培養骨髄幹細胞の静脈内投与 (2010)
  • Author(s): 本望修
  • Organizer: 第255回日本内科学会北海道地方会例会
  • Place of Presentation: 札幌
  • Year and Date: 2010-06-19
• [Presentation] 脳梗塞に対する自己培養骨髄幹細胞の静脈内投与 (2010)
  • Author(s): 本望修
  • Organizer: 第255回 日本内科学会北海道地方会例会
  • Place of Presentation: 札幌
  • Year and Date: 2010-06-19
• [Presentation] 脳神経外科学領域における再生医療の臨床応用の現状 (2010)
  • Author(s): 本望修
  • Organizer: 第35回日本外科系連合学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2010-06-18
• [Presentation] 脳卒中における再生医療の展望 (2010)
  • Author(s): 本望修
  • Organizer: 第30回日本脳神経外科コングレス総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-05-09
• [Presentation] 脳卒中における再生医療の展望 (2010)
  • Author(s): 本望修
  • Organizer: 第30回 日本脳神経外科コングレス総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-05-09
• [Presentation] Intravenous transplantation of autologous mesenchymal stem cells derived from bone marrow into stroke patients, and application for spinal cord injury (2010)
  • Author(s): Honmou O
  • Organizer: The International Conference of Stem Cells & Regenerative Medicine for Neurodegenerative Diseases
  • Place of Presentation: Taiwan
  • Year and Date: 2010-04-23
• [Presentation] Intravenous transplantation of autologous mesenchymal stem cells derived from bone marrow into stroke patients, and application for spinal cord injury. (2010)
  • Author(s): Honmou O
  • Organizer: The International Conference of Stem Cells & Regenerative Medicine for Neurodegenerative Diseases
  • Place of Presentation: Taiwan
  • Year and Date: 2010-04-23
• [Presentation] 脳梗塞に対する二重遺伝子導入ヒト骨髄幹細胞移植による治療 (2009)
  • Author(s): 本望修
  • Organizer: 日本脳神経外科学会第68回学術総会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-14
• [Book] 自己培養骨髄幹細胞の脳梗塞疾患に対する静脈内投与.臨床評価 (2011)
  • Author(s): 本望修
  • Publisher: 統洋社
• [Book] 脳梗塞に対する骨髄幹細胞臨床神経外科Clinical Neuroscience (2011)
  • Author(s): 本望修、佐々木雄一
  • Publisher: 中外医学社
• [Book] 臨床と研究 (2011)
  • Author(s): 本望修
  • Publisher: 大道学館
• [Book] 脳梗塞に対する自己骨髄幹細胞の静脈内投与臨床評価 (2010)
  • Author(s): 本望修, 小野寺理恵
  • Publisher: 統洋社
• [Book] 脳梗塞に対する自己骨髄幹細胞の静脈内投与(38-3) (2010)
  • Author(s): 本望修, 小野寺理恵
  • Publisher: 臨床評価
• [Book] 脳血管障害の再生医療神経治療学 (2009)
  • Author(s): 本望修
  • Publisher: 公和図書
• [Book] 骨髄幹細胞と神経再生医学のあゆみ (2009)
  • Author(s): 本望修
  • Publisher: 医歯薬出版
• [Book] 神経再生治療-綜合臨牀 (2009)
  • Author(s): 本望修, 宝金清博
  • Publisher: 永井書店
• [Book] 脳梗塞の神経再生医療-医学のあゆみ (2009)
  • Author(s): 本望修, 宝金清博
  • Publisher: 医歯薬出版
• [Book] 白質病変-分子レベルからみた病態,治療の新展開-骨髄幹細胞移植による脳虚血障害の治療-.分子脳血管病 (2009)
  • Author(s): 本望修, 大石美里, 宝金清博
  • Publisher: 先端医学社
• [Book] 脳血管障害の再生医療(26) (2009)
  • Author(s): 本望修
  • Publisher: 神経治療学
• [Book] 骨髄幹細胞と神経再生(231) (2009)
  • Author(s): 本望修
  • Publisher: 医学のあゆみ
• [Book] 神経再生治療(58) (2009)
  • Author(s): 本望修, 宝金清博
  • Publisher: 綜合臨牀
• [Book] 脳梗塞の神経再生医療(231) (2009)
  • Author(s): 本望修, 宝金清博
  • Publisher: 医学のあゆみ
• [Book] 白質病変-分子レベルからみた病態,治療の新展開-骨髄幹細胞移植による脳虚血障害の治療-(8) (2009)
  • Author(s): 本望修, 大石美里, 宝金清博
  • Publisher: 分子脳血管病
• [Book] Neuroscience Research Volume 65(Development of a stroke model in the nonhuman primate and a safety study of IV infusion of human mesenchymal stem cells.) (2009)
  • Author(s): Sasaki M, Radtke C, Honmou O, Houkin K, Kocsis JD
  • Total Pages: 1
  • Publisher: Supplement
• [Book] 最新・脳血管疾患 Update 脳梗塞の神経再生医療 (2009)
  • Author(s): 本望修
  • Total Pages: 588
  • Publisher: 医歯薬出版株式会社
• [Book] 骨髄幹細胞を用いた脳梗塞の治療.脳外誌 (2008)
  • Author(s): 本望修, 宝金清博
  • Publisher: 医学書院
• [Book] 脳梗塞急性期の治療(4)再生医療(骨髄移植を中心に).神経治療学 (2008)
  • Author(s): 本望修, 宝金清博
  • Publisher: 公和図書
• [Book] 再生医療-脳卒中-. Clinical Rehabilitation (2008)
  • Author(s): 本望修
  • Publisher: 医歯薬出版
• [Book] 骨髄由来中胚葉系幹細胞による脳梗塞の治療. Drug Delivery System (2008)
  • Author(s): 本望修
  • Publisher: 日本医学社
• [Book] 骨髄幹細胞を用いた脳梗塞の治療(17) (2008)
  • Author(s): 本望修, 宝金清博
  • Publisher: 脳外誌
• [Book] 脳梗塞急性期の治療(4)再生医療(骨髄移植を中心に)(25) (2008)
  • Author(s): 本望修, 宝金清博
  • Publisher: 神経治療学
• [Book] 再生医療-脳卒中-(17) (2008)
  • Author(s): 本望修
  • Publisher: Clinical Rehabilitation
• [Book] 骨髄由来中胚葉系幹細胞による脳梗塞の治療(23) (2008)
  • Author(s): 本望修
  • Publisher: Drug Delivery System
• [Book] 脳卒中に対する再生医療の展望 (2008)
  • Author(s): 本望 修
  • Total Pages: 2
  • Publisher: 文光堂 Medical Practice
• [Patent(Industrial Property Rights)] 細胞増殖方法ならびに組織の修復および再生のための医薬 (2012)
  • Inventor(s): 本望修ら
  • Industrial Property Rights Holder: 札幌医科大学
  • Acquisition Date: 2012-03-02
• [Patent(Industrial Property Rights)] 細胞懸濁液調製用デバイス (2010)
  • Inventor(s): 本望修
  • Industrial Property Rights Holder: 札幌医科大学
  • Industrial Property Number: 2010-174903
  • Filing Date: 2010-08-03
• [Patent(Industrial Property Rights)] 血液採取キット (2010)
  • Inventor(s): 本望修ら
  • Industrial Property Rights Holder: 札幌医科大学、ニプロ株式会社
  • Industrial Property Number: 2010-174902
  • Filing Date: 2010-08-03
• [Patent(Industrial Property Rights)] 血液採取キット (2010)
  • Inventor(s): 本望修, ら
  • Industrial Property Rights Holder: 札幌医科大学、ニプロ株式会社
  • Industrial Property Number: 2010-174902
  • Filing Date: 2010-08-03
• [Patent(Industrial Property Rights)] 細胞増殖方法ならびに組織の修復および再生のための医薬 (2008)
  • Inventor(s): 本望修ら
  • Industrial Property Rights Holder: 札幌医科大学
  • Filing Date: 2008-09-10
• [Patent(Industrial Property Rights)] 細胞増殖方法ならびに組織の修復および再生のための医薬 (2008)
  • Inventor(s): 本望修, ら
  • Industrial Property Rights Holder: 札幌医科大学
  • Filing Date: 2008-09-10
  • Acquisition Date: 2012-03-02
• [Patent(Industrial Property Rights)] 細胞増殖方法ならびに組織の修復および再生のための医薬 (2008)
  • Inventor(s): 本望修, ら
  • Industrial Property Rights Holder: 札幌医科大学
  • Filing Date: 2008-09-10
• [Patent(Industrial Property Rights)] 細胞増殖方法ならびに組織の修復および再生のための医薬 (2008)
  • Inventor(s): 本望 修
  • Industrial Property Rights Holder: 札幌医科大学
  • Filing Date: 2008-09-10
  • Overseas