Details of a Researcher

Stem Cell Therapy for Dementia

本望修

Brain and nerve : 神経研究の進歩 ( 医学書院 ) 67 ( 1 ) 93 - 98 2015.01

Spinal regeneration by intravenous administration of autologous mesenchymal stem cells

アルツハイマー病トランスジェニックモデルマウスにおける脳内グリア細胞の動態解析

松村晃寛, 鈴木紘美, 大橋乃理子, 鈴木秀一郎, 山内理香, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊, 佐々木祐典, 本望修, 三國信啓, 高田和幸, 北村佳久

臨床神経学 ( (一社)日本神経学会 ) 53 ( 12 ) 1483 - 1483 2013.12

神経保護と神経再生ラット脳梗塞モデルに対する骨髄間葉系幹細胞移植後のfMRIによる皮質賦活信号と運動機能改善との関連性

中崎公仁, 鈴木淳平, 小野寺理恵, 佐々木優子, 岡真一, 佐々木祐典, 本望修

脳循環代謝 ( 日本脳循環代謝学会 ) 25 ( 1 ) 108 - 108 2013.11

本望修, 佐々木祐典, 岡真一

整形・災害外科 ( 金原出版 ) 56 ( 9 ) 1177 - 1181 2013.08

骨髄間葉系幹細胞を用いた脳梗塞の細胞治療 (特集脳卒中診療の最新情報)

脳低温療法を更に普及するための展望再生医療心肺停止後全脳虚血に対する骨髄幹細胞の静脈内投与による治療法の検討

佐々木祐典, 小野寺理恵, 岡真一, 佐々木優子, 中崎公仁, 中村秀之, 山崎弥生, 須永隆文, 泉佳代子, 本望修

日本脳低温療法学会プログラム・抄録集 ( 日本脳低温療法・体温管理学会 ) 16回 41 - 41 2013.07

岡真一, 佐々木祐典, 本望修

臨牀と研究 ( 大道学館出版部 ) 90 ( 6 ) 791 - 796 2013.06

アルツハイマー病トランスジェニックモデルマウスにおける脳内グリア細胞の動態解析

日本神経学会学術大会プログラム・抄録集 54th 369 2013

Bone marrow stem cell therapy for stroke

脳内アミロイドβに対する脳内グリア細胞の動態解析

松村晃寛, 鈴木紘美, 松下隆司, 鈴木秀一郎, 林貴士, 保月隆良, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊, 本望修, 高田和幸, 北村佳久

臨床神経学 ( (一社)日本神経学会 ) 52 ( 12 ) 1582 - 1582 2012.12

救急領域における再生医療の現況再生医療における医師主導治験の推進

小野寺理恵, 佐々木優子, 佐々木祐典, 本望修

日本救急医学会雑誌 ( (一社)日本救急医学会 ) 23 ( 10 ) 453 - 453 2012.10

救急領域における再生医療の現況脳神経疾患に対する自己培養骨髄間葉系幹細胞の静脈内投与

本望修, 佐々木祐典, 佐々木優子, 小野寺理恵

日本救急医学会雑誌 ( (一社)日本救急医学会 ) 23 ( 10 ) 453 - 453 2012.10

岡真一, 佐々木祐典, 本望修

救急医学 ( へるす出版 ) 36 ( 8 ) 982 - 986 2012.08

Mesenchymal stem cells: therapeutic outlook for stroke

Osamu Honmou, Rie Onodera, Masanori Sasaki, Stephen G. Waxman, Jeffery D. Kocsis

TRENDS IN MOLECULAR MEDICINE 18 ( 5 ) 292 - 297 2012.05

Book review, literature introduction, etc.

脳内アミロイドβに対する脳内グリア細胞の動態解析

松村晃寛, 鈴木紘美, 松下隆司, 鈴木秀一郎, 林貴士, 保月隆良, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊, 本望修, 高田和幸, 北村佳久

日本神経学会学術大会プログラム・抄録集 53rd 423 2012

Future Prospective of Stem Cell Therapy for Stroke

HONMOU Osamu

Japanese journal of neurosurgery ( The Japanese Congress of Neurological Surgeons ) 20 ( 8 ) 574 - 579 2011.08

The intravenous administration of mesenchymal stem cells (MSCs) derived from bone marrow has been reported to ameliorate functional deficits in several CNS diseases in experimental animal models. Although MSCs may be present in different proportions in the stromal cell fraction of various species, human MSCs have a distinct cell surface antigen pattern including SH2^+, SH3^+, and CD34^-. Although human MSCs have been clinically used for treating several diseases, it is still uncertain whether MSCs may have therapeutic benefits for stroke patients. The objectives of this study were to examine the feasibility and safety of cell therapy using auto serum expanded autologous MSCs in stroke patients. Twelve (male and female) patients with stroke were enrolled. Bone marrow from the stroke patients were obtained by aspiration from the posterior iliac crest after informed consent was obtained. MSCs were cultured in appropriate medium in a humidified atmosphere of 5% CO_2 at 37℃, harvested, and cryopreserved until use. On the day of infusion cryopreserved units were thawed and injected intravenously into patients over 30min. All patients were monitored closely during and within 48h of MSC injections. Oxygen saturation, temperature, blood pressure, pulse and respiratory rate were carefully monitored before and after injection. Patients also had chest films before and after MSC injection. Patients had carefully been followed for 12 months. Human bone marrow-derived MSCs were successfully isolated from bone marrow aspirate from all 12 stroke patients, and all were successfully culture-expanded. Serial evaluations showed no severe adverse cell-related effects. In patients with cerebral infarcts, the intravenous administration of autologous MSCs appears to be feasible and safe, and merits further study as a therapy that may improve functional recovery.

Remyelination after olfactory ensheathing cell transplantation into diverse demyelinating environments

Masanori Sasaki, Karen L. Lankford, Christine Radtke, Osamu Honmou, Jeffery D. Kocsis

EXPERIMENTAL NEUROLOGY 229 ( 1 ) 88 - 98 2011.05

Book review, literature introduction, etc.

インビトロ血液脳関門モデルを用いた骨髄幹細胞の分子・細胞動態解析系の構築

松下隆司, 片山貴博, 木林達也, 鈴木秀一郎, 川又純, 本望修, 南雅文, 下濱俊

日本神経学会学術大会プログラム・抄録集 52nd 375 2011

脳虚血に対する幹細胞移植

本望修

No Shinkei Geka 38 515 - 520 2010

Stem cell therapy

本望修, 宝金清博

医学のあゆみ ( 医歯薬出版 ) 231 ( 5 ) 553 - 556 2009.10

【脳卒中診療のトピックス脳卒中治療ガイドライン2009の登場に当たって】脳梗塞治療の将来展望

Intravenous administration of autologous mesenchymal stem cells derived from bone marrow into stroke patients

K. Houkin, O. Honmou, T. Matsunaga, S. Ishiai, S. Waxman, J. Kocsis

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 29 S560 - S560 2009.10

Research paper, summary (international conference)

本望修, 宝金清博

Progress in Medicine ( (株)ライフ・サイエンス ) 29 ( 9 ) 2209 - 2213 2009.09

脳卒中治療に再生医療は役立つか (特集脳卒中診療Up-date--脳卒中の発症予防,急性期治療から再発予防まで)

本望修, 寶金清博

成人病と生活習慣病 ( 東京医学社 ) 39 ( 8 ) 929 - 932 2009.08

【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

本望修, 大石美里, 宝金清博

分子脳血管病 ( (株)先端医学社 ) 8 ( 2 ) 169 - 172 2009.04

A cell therapy for stroke

本望修, 宝金清博

綜合臨床 ( 永井書店 ) 58 ( 2 ) 217 - 220 2009.02

Development of a stroke model in the nonhuman primate and a safety study of IV infusion of human mesenchymal stem cells

Masanori Sasaki, Christine Radtke, Osamu Honmou, Kiyohiro Houkin, Jeffery Kocsis

NEUROSCIENCE RESEARCH 65 S127 - S127 2009

Research paper, summary (international conference)

1-5-28 骨髄幹細胞を用いた脳梗塞治療に適した機能評価法の検討 : 第1報(脳卒中(評価(2)),口演,一般演題,リハビリテーション医学の進歩"評価から治療介入へ",第45回日本リハビリテーション医学会学術集会)

本望修, 宝金清博

Medical Practice ( (株)文光堂 ) 25 ( 12 ) 2237 - 2238 2008.12

A Bone Marrow Stem Cell Therapy for Stroke Patients(<SPECIAL ISSUES>Reconstruction of Neural Function : Its Clinical Application)

Honmou Osamu, Houkin Kiyohiro

Japanese journal of neurosurgery ( 日本脳神経外科コングレス ) 17 ( 7 ) 527 - 530 2008.07

Stem cells or progenitors derived from non-neural samples as well as neural tissues in humans are thought to be a good candidate for use in regenerative medicine in CNS diseases. The characteristics of these stem cells include a high proliferating potential and multipotential. They show good adaptation in the host's central nervous system (CNS), migrate through the normal and damaged brain tissue, and differentiate in the host's microenvironment subsequent to transplantation. These characteristics seem to be very useful in establishing a cell therapy for CNS diseases. A distinct advantage o...

DOI CiNii

石合純夫, 本望修, 寶金清博, 森泉茂宏, 土岐めぐみ, 村上孝徳, 本間真理

リハビリテーション医学 : 日本リハビリテーション医学会誌 ( 社団法人日本リハビリテーション医学会 ) 45 S171 2008.05

Intravenous transplantation of autologous mesenchymal stem cells derived from bone marrow into stroke patients

Osamu Honmou, Kiyohiro Houkin, Takuya Matsunaga, Yoshiro Niitsu, Sumio Ishiai, Stephen G. Waxman, Jeffery D. Kocsis

STROKE 39 ( 2 ) 543 - 543 2008.02

Research paper, summary (international conference)

脳梗塞に対するヒト骨髄幹細胞の多数回移植による治療効果の検討

大森義範, 本望修, 鈴木淳平, 宝金清博

日本脳神経外科学会総会CD-ROM抄録集 ( (一社)日本脳神経外科学会 ) 66回 2K - 7 2007.10

脳梗塞に対するAng-1-VEGF産生ヒト骨髄幹細胞移植による血管新生の検討

外山賢太郎, 本望修, 鈴木淳平, 宝金清博, 濱田洋文

日本脳神経外科学会総会CD-ROM抄録集 ( (一社)日本脳神経外科学会 ) 66回 2K - 2 2007.10

脳梗塞に対する骨髄幹細胞治療

本望修, 寳金清博

脳卒中 29 ( 2 ) 2007

血管病変への再生医療 : 2)脳血管障害に対する再生医療

本望修, 宝金清博

糖尿病 = Journal of the Japan Diabetes Society 49 ( 12 ) 911 - 913 2006.12

DOI CiNii J-GLOBAL

脳梗塞におけるGDNF産生ヒト骨髄間葉系幹細胞の経静脈的移植による治療効果の検討

堀田祥史, 本望修, 原田邦明, 寶金清博, 濱田洋文

脳卒中 28 ( 4 ) 2006.12

脳血管障害総論 XI.治療動向開発・研究中の遺伝子治療,再生医療各論脳梗塞の細胞療法(神経再生治療)-自家骨髄細胞の静脈内投与-

本望修, 寳金清博

日本臨床 64 2006

A Cell Therapy for Stroke

HONMOU Osamu

理学療法 = Journal of physical therapy 22 ( 12 ) 1548 - 1551 2005.12

The Journal of Gene Medicine Japanese Society of Gene Therapy Young Investigator Award 2005 - Kazuhiko Kurozumi, Department of Neurological Surgery, Ohio State University Medical Center, USA

K Kurozumi, K Nakamura, T Ichikawa, T Tamiya, Y Ito, O Honmou, K Houkin, H Hamada, Date, I

JOURNAL OF GENE MEDICINE 7 ( 12 ) 1586 - 1587 2005.12

Other

【脳循環代謝の分子イメージングの進歩】再生医療と分子イメージング

迷走神経刺激療法が著効したLennox-Gastaut症候群の1女児例

若井周治, 二階堂弘輝, 堤裕幸, 本望修, 宝金清博, 川本芳誉

日本小児科学会雑誌 ( (公社)日本小児科学会 ) 109 ( 7 ) 860 - 860 2005.07

原田邦明, 本望修, 宝金清博

分子脳血管病 ( (株)先端医学社 ) 4 ( 3 ) 293 - 297 2005.07

Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene therapy

H Hamada, M Kobune, K Nakamura, Y Kawano, K Kato, O Honmou, K Houkin, T Matsunaga, YN Niitsu

CANCER SCIENCE ( BLACKWELL PUBLISHING INC ) 96 ( 3 ) 149 - 156 2005.03

Book review, literature introduction, etc.

We developed human mesenchymal stem cell (MSC) lines that could differentiate into various tissue cells including bone, neural cells, bone marrow (BM) stromal cells supporting the growth of hematopoietic stem cell (HSC), and so-called 'tumor stromal cells' mixing with tumor cells. We investigated the applicability of MSC as therapeutic cell transplanting reagents (cytoreagents). Telomerized human BM derived stromal cells exhibited a prolonged lifespan and supported the growth of hematopoietic clonogenic cells. The gene transfer of Indian hedgehog (Ihh) remarkably enhanced the HSC expansion supported by the human BM stromal cells. Gene-modified MSC are useful as therapeutic tools for brain tissue damage (e.g. brain infarction) and malignant brain neoplasms. MSC transplantation protected the brain tissue from acute ischemic damage in the midcerebral artery occlusion (MCAO) animal model. Brain-derived neurotrophic factor (BDNF)-gene transduction further enhanced the protective efficacy against the ischemic damage. MSC possessed excellent migratory ability and exerted inhibitory effects on the proliferation of glioma cells. Gene-modification of MSC with therapeutic cytokines clearly augmented the antitumor effect and prolonged the survival of tumor-bearing animals. Gene therapy employing MSC as a tissue-protecting and targeting cytoreagent would be a promising approach.

DOI PubMed

【脳卒中基礎研究と臨床の最前線】基礎研究の現況と将来展望細胞移植と脳卒中

宝金清博, 本望修

医学のあゆみ ( 医歯薬出版(株) ) 212 ( 6 ) 569 - 574 2005.02

Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model

K Kurozumi, K Nakamura, T Tamiya, Y Kawano, K Ishii, M Kobune, S Hirai, H Uchida, K Sasaki, Y Ito, K Kato, O Honmou, K Houkin, Date, I, H Hamada

MOLECULAR THERAPY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 11 ( 1 ) 96 - 104 2005.01

Mesenchymal stem cells (MSC) were reported to ameliorate functional deficits after stroke in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. To enhance such cytokine effects, we previously transfected the telomerized human MSC with the BDNF gene using a fiber-mutant adenovirus vector and reported that such treatment contributed to improved ischemic recovery in a rat transient middle cerebral artery occlusion (MCAO) model. In the present study, we investigated whether other cytokines in addition to BDNF, i.e., GDNF, CNTF, or NT3, might have a similar or greater effect in this model. Rats that received MSC-BDNF (P < 0.05) or MSC-GDNF (P < 0.05) showed significantly more functional recovery as demonstrated by improved behavioral test results and reduced ischemic damage on MRI than did control rats 7 and 14 days following MCAO. On the other hand, rats that received MSC-CNTF or MSC-NT3 showed neither functional recovery nor ischemic damage reduction compared to control rats. Thus, MSC transfected with the BDNF or GDNF gene resulted in improved function and reduced ischemic damage in a rat model of MCAO. These data suggest that gene-modified cell therapy may be a useful approach for the treatment of stroke.

Autologous transplantation of expanded neural precursor cells into the demyelinated monkey spinal cord

S Oka, O Honmou, Y Akiyama, M Sasaki, K Houkin, K Hashi, JD Kocsis

BRAIN RESEARCH ( ELSEVIER SCIENCE BV ) 1030 ( 1 ) 94 - 102 2004.12

The objective of this study was to establish if neural precursor cells could safely be developed from biopsy of the subventricular zone (SVZ) in the non-human primate (marmoset), and to determine their myelinating potential after autologous transplantation into a demyelinated lesion. Small amounts of tissue were safely collected from the subventricular-subependymal zone of the adult primate brain under ultrasonography without any neurological deficit. Neural precursor cells were isolated and expanded in the presence of mitogen in vitro. The dorsal columns of the adult marmoset spinal cord were demyelinated by X-irradiation and intraspinal injections of ethidium bromide in the center of the radiation field. Cell suspensions of the neural precursors were microinjected through a micropipette into the demyelinated lesion site in the spinal cord. Lesions were histologically examined 3 weeks after transplantation. Light and electron microscopic examination of plastic embedded sections revealed a significant number of myelinating profiles in the transplantation zone; no myelination was observed in control lesions. The myelinated axons had predominantly peripheral patterns of myelination. These results demonstrate that autologous transplantation of neural precursor cells in the adult nonhuman primate can remyelinate demyelinated central nervous system (CNS) axons, thus suggesting the potential utility of such an approach in demyelinating lesions in humans. (C) 2004 Elsevier B.V. All rights reserved.

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

K Nakamura, Y Ito, Y Kawano, K Kurozumi, M Kobune, H Tsuda, A Bizen, O Honmou, Y Niitsu, H Hamada

GENE THERAPY ( NATURE PUBLISHING GROUP ) 11 ( 14 ) 1155 - 1164 2004.07

The prognosis of patients with malignant glioma is extremely poor, despite the extensive surgical treatment that they receive and recent improvements in adjuvant radio- and chemotherapy. In the present study, we propose the use of gene-modified mesenchymal stem cells (MSCs) as a new tool for gene therapy of malignant brain neoplasms. Primary MSCs isolated from Fischer 344 rats possessed excellent migratory ability and exerted inhibitory effects on the proliferation of 9L glioma cell in vitro. We also confirmed the migratory capacity of MSCs in vivo and showed that when they were inoculated into the contralateral hemisphere, they migrated towards 9L glioma cells through the corpus callosum. MSCs implanted directly into the tumor localized mainly at the border between the 9L tumor cells and normal brain parenchyma, and also infiltrated into the tumor bed. Intratumoral injection of MSCs caused significant inhibition of 9L tumor growth and increased the survival of 9L glioma-bearing rats. Gene-modification of MSCs by infection with an adenoviral vector encoding human interleukin-2 (IL-2) clearly augmented the antitumor effect and further prolonged the survival of tumor-bearing rats. Thus, gene therapy employing MSCs as a targeting vehicle would be promising as a new therapeutic approach for refractory brain tumor.

脳神経外科における産学官連携

本望修, 宝金清博

Neurological Surgery ( (株)医学書院 ) 32 ( 6 ) 571 - 577 2004.06

A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats

S Iihoshi, O Honmou, K Houkin, K Hashi, JD Kocsis

BRAIN RESEARCH ( ELSEVIER SCIENCE BV ) 1007 ( 1-2 ) 1 - 9 2004.05

The primary objective of this study was to test the hypothesis that intravenous administration of autologous bone marrow cells could improve functional recovery after middle cerebral artery occlusion (MCAO) for 45 min in the rat and to determine specific time windows for efficacy. Mononuclear cells from autologous bone marrow were transfected with the LacZ reporter gene, and injected intravenously into rats at 3-72 h after induction of MCAO. Histological analysis of the ischemic lesion at 14 days after transplantation revealed reduced ischemic lesion volume. Lesion volume was 250 +/- 45 mm(3) (n = 6) after MCAO without cell transplantation. Lesions were minimally detected by absence of 2,3,5-triphenyltetrazolium chloride (TTC) staining when bone marrow cells were infused 3 h after lesion induction. Lesions were clearly detected beginning with the 6-h postlesion group and became progressively larger at 12, 24 and 72 h (80 +/- 25, 140 +/- 18, and 180 +/- 22 mm(3), respectively; n=6 for each group). Transplanted LacZ(+) bone marrow cells accumulated extensively in and around the ischemic lesions, and immunohistochemistry suggests some neuronal and glial lineage differentiation. Behavioral testing (Morris water maze and Treadmill stress test) indicated greater functional recovery in the treated group. These findings suggest that early intervention with intravenous administration of autologous mononuclear cells from bone marrow can reduce lesion size in the MCAO model in the rat, and improve functional outcome. (C) 2004 Elsevier B.V. All rights reserved.

BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model (vol 9, pg 189, 2004)

K Kurozumi, K Nakamura, T Tamiya, Y Kawano, M Kobune, S Hirai, H Uchida, K Sasaki, Y Ito, K Kato, O Honmou, K Houkin, Date, I, H Hamada

MOLECULAR THERAPY 9 ( 5 ) 766 - 766 2004.05

Other

Cytokine gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model

K Kurozumi, K Nakamura, T Ichikawa, Y Ono, T Tamiya, Y Ito, O Honmou, K Houkin, H Hamada, Date, I

MOLECULAR THERAPY 9 S20 - S20 2004.05

Research paper, summary (international conference)

BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model

K Kurozumi, K Nakamura, T Tamiya, Y Kawano, M Kobune, S Hirai, H Uchida, K Sasaki, Y Ito, K Kato, O Honmou, K Houkin, Date, I, H Hamada

MOLECULAR THERAPY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 9 ( 2 ) 189 - 197 2004.02

Examination of the clinical therapeutic efficacy of using bone marrow stromal cells, including mesenchymal stem cells (MSC), has recently been the focus of much investigation. MSC were reported to ameliorate functional deficits after stroke in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. To enhance such cytokine effects, we transfected telomerized human MSC with the BDNF gene using a fiber-mutant F/RGD adenovirus vector and investigated whether these cells contributed to improved functional recovery in a rat transient middle cerebral artery occlusion (MCAO) model. BDNF production by MSC-BDNF cells was 23-fold greater than that seen in uninfected MSC. Rats that received MSC-BDNF showed significantly more functional recovery than did control rats following MCAO. Specifically, MRI analysis revealed that the rats in the MSC-BDNF group exhibited more significant recovery from ischemia after 7 and 14 days. The number of TUNEL-positive cells in the ischemic boundary zone was significantly smaller in animals treated with MSC-BDNF compared to animals in the control group. These data suggest that MSC transfected with the BDNF gene may be useful in the treatment of cerebral ischemia and may represent a new strategy for the treatment of stroke.

[Consequence of intellectual property and consortium project in neurosurgery]

Osamu Honmou, Kiyohiro Houkin

No Shinkei Geka 32 ( 6 ) 571 - 7 2004 [Domestic journal]

PubMed

Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord

M Inoue, O Honmou, S Oka, K Houkin, K Hashi, JD Kocsis

GLIA ( WILEY-LISS ) 44 ( 2 ) 111 - 118 2003.11

The remyelinating potential of autologous bone marrow cells was studied after direct injection and following intravenous injection into rats with a demyelinated lesion in the spinal cord. Both focal and intravenous injections of acutely isolated mononuclear bone marrow cell fractions resulted in varying degrees of remyelination. Suspensions of bone marrow cells collected from the same rat were delivered at varied concentrations (10(2) to 10(5) for direct injection and 10(4) to 10(7) for i.v. injections). The lesions were examined histologically 3 weeks after transplantation. Light microscopic examination revealed remyelination in the dorsal funiculus with both injection protocols, but the extent of remyelination was proportional to the number of injected cells. To attain the same relative density of remyelination achieved by direct injection, intravenous administration of cells required delivery of substantially more cells (two orders of magnitude). However, the availability of autologous bone marrow cells in large number and the potential for systemically delivering cells to target lesion areas without neurosurgical intervention suggest the potential utility of intravenous cell delivery as a prospective therapeutic approach in demyelinating disease. (C) 2003 Wiley-Liss, Inc.

Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells

M Kobune, Y Kawano, Y Ito, H Chiba, K Nakamura, H Tsuda, K Sasaki, H Dehari, H Uchida, O Honmou, S Takahashi, A Bizen, R Takimoto, T Matsunaga, J Kato, K Kato, K Houkin, Y Niitsu, H Hamada

EXPERIMENTAL HEMATOLOGY ( ELSEVIER SCIENCE INC ) 31 ( 8 ) 715 - 722 2003.08

Objective. To compare the hematopoietic support provided by telomerized human mesenchymal stem cells (MSCs) and telomerized MSC-derived stromal cells. Methods. We transfected the human telomerase catalytic subunit (hTERT) gene into primary MSCs to establish hTERT-transduced MSCs (hTERT-MSCs). Stromal induction of hTERT-MSCs was performed by replacing the culture medium with Dexter-type culture medium. Hematopoietic support was examined by coculture with cord blood CD34(+) cells. Results. The hTERT-MSCs were morphologically identical with the primary MSCs and expressed surface antigens including CD105, CD73, and CD166. hTERT-MSCs showed a similar doubling time as primary MSCs and continued to proliferate to over 80 population doublings (PD), although the primary MSCs underwent crisis in vitro at 16 PD. The osteogenic, chondrogenic, adipogenic, neurogenic, and stromal differentiation potential of hTERT-MSCs were maintained up to at least 40 PD. The degree of expansion of CD34+ cells and total number of colony-forming units in culture (CFU-C) upon 12-day coculture with the hTERT-MSC-derived stromal cells were nearly the same as those upon 12-day coculture with hTERT-MSCs (CD34, 33.0-fold +/- 2.8-fold vs 36.1-fold +/- 1.7-fold of the initial cell number; CFUs, 344.4-fold +/- 62.5-fold vs 239.3-fold +/- 87.0-fold; CFU-mix, 368.4-fold +/- 113.7-fold vs 341.3-fold +/- 234.3-fold). However, on day 18 of coculture, the number of cobblestone areas (CA) observed beneath the stromal cells was 15 times higher than that beneath hTERT-MSCs (CA, 146.9 +/- 54.6 vs 9.4 +/- 8.1, p < 0.01). Conclusion. Stromal induction of hTERT-MSCs exclusively enhanced the support of CA formation provided by hTERT-MSCs. Our human hTERT-MSCs will be useful for elucidating the mechanism of the formation of CAs. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc.

Awake surgeryによる運動性言語領野の同定の試み

Differential gene expression screening between parental and highly metastatic pancreatic cancer variants using a DNA microarray

H Tanaka, F Hata, H Nishimori, O Honmou, T Yasoshima, H Nomura, K Ohno, Hirai, I, K Kamiguchi, H Isomura, Y Hirohashi, R Denno, N Sato, K Hirata

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 22 ( 2 ) 307 - 313 2003.06

迷走神経刺激療法が著効したLennox-Gastaut症候群の1女児例

若井周治, 二階堂弘輝, 堤裕幸, 本望修, 宝金清博, 川本芳誉

日本小児科学会雑誌 ( (公社)日本小児科学会 ) 107 ( 5 ) 849 - 849 2003.05

本望修, 鰐淵昌彦, 南田善弘, 田邊純嘉, 宝金清博

臨床神経生理学 ( (一社)日本臨床神経生理学会 ) 31 ( 2 ) 216 - 216 2003.04

神経幹細胞移植

Clin Ｎeurosci 21 542 - 542 2003

細胞移植療法による神経再生戦略

最新医学 58 677 - 684 2003

神経再生医療の基礎知識

脊椎脊髄ジャーナル 16 101 - 105 2003

Transplantation of mesenchymal stem cells derived from the bone marrow into the demyelinated spinal cord

A Bizen, O Honmou, M Inoue, S Iihoshi, K Houkin, K Hashi

MOLECULAR MECHANISMS AND EPOCHAL THERAPEUTICS OF ISCHEMIC STROKE AND DEMENTIA 1252 471 - 475 2003

脳卒中に対する再生医療の展望

最新医学 58 899 - 903 2003

Pharmacology of Cerebral Ischemia

2003

中枢性脱髄疾患に対する胚性幹細胞・骨髄の移植.

脳の科学「神経の再生」 2003

Transplantation of neural stem cell into ischemic brain

International Congress Series 2003

脳梗塞への幹細胞移植

分子脳血管病 2 426 - 431 2003

ヒト胎児脳、成人脳、骨髄細胞のラットへの移植

Clin Neurosci 21 1155 - 1157 2003

神経幹細胞移植のソース

脳の科学「神経の再生」 2003

島根医学別冊

23 73 - 73 2003

胚性幹細胞療法

先端医療シリーズ18・脳神経外科脳腫瘍の最新医療 2003

神経の再生戦略

Surgery Frontier 10 43 - 48 2003

脳梗塞の幹細胞移植治療

分子脳血管病 2 333 - 337 2003

Transplantation of human neural stem cells into the stroke model

HONMOU Osamu, OKA Shinichi, SASAKI Masanori, TAKAHASHI Akira, TANOOKA Atsushi, HOUKIN Kiyohiro, HASHI Kazuo

Nosotchu 24 ( 3 ) 355 - 358 2002.09

DOI CiNii J-GLOBAL

Remyelination of the spinal cord following intravenous delivery of bone marrow cells

Y Akiyama, C Radtke, O Honmou, JD Kocsis

GLIA ( WILEY-LISS ) 39 ( 3 ) 229 - 236 2002.09

Bone marrow contains a population of pluripotent cells that can differentiate into a variety of cell lineages, including neural cells. When injected directly into the demyelinated spinal cord they can elicit remyelination. Recent work has shown that following systemic delivery of bone marrow cells functional improvement occurs in contusive spinal cord injury and stroke models in rat. We report here that secondary to intravenous introduction of an acutely isolated bone marrow cell fraction (mononuclear fraction) from adult rat femoral bones separated on a density gradient, ultrastructurally defined remyelination occurs throughout a focal demyelinated spinal cord lesion. The anatomical pattern of remyelination was characteristic of both oligodendrocyte and Schwann cell myelination; conduction velocity improved in the remyelinated axons. When the injected bone marrow cells were transfected to express LacZ, beta-galactosidase reaction product was observed in some myelin-forming cells in the spinal cord. Intravenous injection of other myelin-forming cells (Schwann cells and olfactory ensheathing cells) or the residual cell fraction of the gradient did not result in remyelination, suggesting that remyelination was specific to the delivery of the mononuclear fraction. While the precise mechanism of the repair, myelination by the bone marrow cells or facilitation of an endogenous repair process, cannot be fully determined, the results demonstrate an unprecedented level of myelin repair by systemic delivery of the mononuclear cells.

International cooperation to run a brain bank: Austro-German-Japanese (AGJ) brain bank

E Hashimoto, H Ozawa, O Honmou, K Hashi, G Murakami, T Saito, R Riederer

INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY 17 S137 - S137 2002.08

Research paper, summary (international conference)

In-111-DTPA cisterno SPECT for the diagnosis of CSF rhinorrhea: Case report

T Yonemori, H Karibe, F Matsuno, O Honmou, Y Minamida, T Uede, S Tanabe, K Hashi

NEUROLOGICAL SURGERY 30 ( 6 ) 617 - 621 2002.06

A quantitative morphometric analysis of rat spinal cord remyelination following transplantation of allogenic Schwann cells

KL Lankford, T Imaizumi, O Honmou, JD Kocsis

JOURNAL OF COMPARATIVE NEUROLOGY ( WILEY-LISS ) 443 ( 3 ) 259 - 274 2002.02

Quantitative morphometric techniques were used to assess the extent and pattern of remyelination produced by transplanting allogenic Schwann cells into demyelinated lesions in adult rat spinal cords. The effects of donor age, prior culturing of donor cells, prior lesioning of donor nerves, and host immunosuppression were evaluated by transplanting suspensions of 30,000 acutely dissociated or cultured Schwann cells from neonatal, young adult, or aged adult rat sciatic nerves into X-irradiation and ethidium bromide-induced demyelinated dorsal column lesions, with or without co-transplantation of neonatal optic nerve astrocytes. Three weeks after transplantation, spinal cords were processed for histological analysis. Under all Schwann cell transplant protocols, large areas containing many Schwann cell-like myelinated axon profiles could be readily observed throughout most of the lesion length. Within these "myelin-rich" regions, the vast majority of detectable axons showed a peripheral-like pattern of myelination. However, interaxonal spacing also increased, resulting in densities of myelinated axons that were more similar to peripheral nerve than intact dorsal columns. Freshly isolated Schwann cells remyelinated more axonal length than cultured Schwann cells, and cells from younger donors remyelinated slightly more axon length than cells from older donors, but all Schwann cell transplant protocols remyelinated tens of thousands of millimeters of axon length and remyelinated axons at similar densities. These results indicate that Schwann cells prepared under a variety of conditions are capable of eliciting remyelination, but that the density of remyelinated axons is much lower than the myelinated axon density in intact spinal cords. J. Comp. Neurol. 443:259-274, 2002. (C) 2002 Wiley-Liss, Inc.

新専門医によるreview 専門医に求められる最新の知識。神経幹細胞。

Intravenous administration of autologous bone marrow cells repairs the ischemic lesions in the rat middle cerebral artery occlusion model

Abst. Society for Neuroscience 2002

脳血管障害の再生医療の展望

循環器 New Trendsシリーズ6 脳血管障害-急性期治療から予防まで− 2002

Comparison of remyelination in the remyelination in the focal transplantation and the intravenous administration of autologous bone marrow cells into the rat demyelinated model.

Abst. Society for Neuroscience 2002

光リソグラフィーによるヒト神経幹細胞の遺伝子解析

CI研究 2002

Transplantation of the embryonic stem cells into the ischemic brain

Restorative Neurology and Neuroscience 2002

神経幹細胞移植

脳神経外科速報 12 331 - 336 2002

骨髄細胞を用いた神経再生医療

Restorative Neurology and Neuroscience 2002

井上道夫

脳神経外科速報 12 331 - 336 2002

ヒト成熟脳由来クローン化神経幹細胞の移植による末梢性髄鞘の再形成

Clinical Neuroscience 20 79 - 81 2002

神経機能回復へ向けた神経幹細胞移植研究

先端医療シリーズ16・脳神経外科機能的脳神経外科の最先端 2002

脳血管障害の再生医療の展望

循環器 New Trendsシリーズ「脳血管障害—急性期治療から予防まで」 6 37 - 45 2002

AHA 未破裂脳動脈瘤ガイドライン

脳卒中ナビゲーター, 診断・治療指針 2002

Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons

M Sasaki, O Honmou, Y Akiyama, T Uede, K Hashi, JD Kocsis

GLIA ( WILEY-LISS ) 35 ( 1 ) 26 - 34 2001.07

The potential of bone marrow cells to differentiate into myelin-forming cells and to repair the demyelinated rat spinal cord in vivo was studied using cell transplantation techniques. The dorsal funiculus of the spinal cord was demyelinated by x-irradiation treatment, followed by microinjection of ethidium bromide. Suspensions of a bone marrow cell fraction acutely isolated from femoral bones in LacZ transgenic mice were prepared by centrifugation on a density gradient (Ficoll-Paque) to remove erythrocytes, platelets, and debris. The isolated cell fraction contained hematopoietic and nonhematopoietic stem and precursor cells and lymphocytes. The cells were transplanted into the demyelinated dorsal column lesions of immunosuppressed rats. An intense blue beta -galactosidase reaction was observed in the transplantation zone. The genetically labeled bone marrow cells remyelinated the spinal cord with predominately a peripheral pattern of myelination reminiscent of Schwann cell myelination. Transplantation of CD34(+) hematopoietic stem cells survived in the lesion, but did not form myelin. These results indicate that bone marrow cells can differentiate in vivo into myelin-forming cells and repair demyelinated CNS. GLIA 35:26-34, 2001. (C) 2001 Wiley-Liss, Inc.

Neural stem cells derived from adult human brain: Implications for a cell therapy for CNS diseases

O Honmou, T Uede, K Hashi

NEUROLOGICAL SURGERY 29 ( 4 ) 293 - 304 2001.04

Transplantation of clonal neural precursor cells derived from adult human brain establishes functional peripheral myelin in the rat spinal cord

Y Akiyama, O Honmou, T Kato, T Uede, K Hashi, JD Kocsis

EXPERIMENTAL NEUROLOGY ( ACADEMIC PRESS INC ) 167 ( 1 ) 27 - 39 2001.01

We examined the myelin repair potential of transplanted neural precursor cells derived from the adult human brain from tissue removed during surgery. Sections of removed brain indicated that nestin-positive cells were found predominately in the subventricular zone around the anterior horns of the lateral ventricle and in the dentate nucleus. Neurospheres were established and the nestin-positive cells were clonally expanded in EGF and bFGF. Upon mitogen withdrawal in vitro, the cells differentiated into neuron- and glia-like cells as distinguished by antigenic profiles; the majority of cells in culture showed neuronal and astrocytic properties with a small number of cells showing properties of oligodendrocytes and Schwann cells. When transplanted into the demyelinated adult rat spinal cord immediately upon mitogen withdrawal, the cells elicited extensive remyelination with a peripheral myelin pattern similar to Schwann cell myelination characterized by large cytoplasmic and nuclear regions, a basement membrane, and PO immunoreactivity. The remyelinated axons conducted impulses at near normal conduction velocities. This suggests that a common neural progenitor cell for CNS and PNS previously described for embryonic neuroepithelial cells may be present in the adult human brain and that transplantation of these cells into the demyelinated spinal cord results in functional remyelination. (C) 2001 Academic Press.

「細胞治療〜再生医療への展開」神経幹細胞移植

最新医学 12 2666 - 2670 2001

AC133-positive cells derived from bone marrow remyelinate demyelinated axons in the adult rat spinal cord. Abst.

Abst. Society for Neuroscience 0 0-0 2001

Excitatory and inhibitory responses and synaptic transmission differentiated from the adult human neural stem cells in vitro.

Restorative Neurology and Neuroscience. 17 152 - 152 2001

未破裂動脈瘤への対応

本望修, 上出廷治, 端和夫

診断と治療 ( 診断と治療社 ) 89 ( 11 ) 2047 - 2052 2001

Neural reconstruction by transplantation of clonal neural stem cells derived from adult human brain : implications for a cell therapy for Parkinson disease

神経疾患の神経幹細胞治療—動物モデルでの試み

脳の科学 23 127 - 132 2001

脳神経疾患と神経再生

脳の科学 23 587 - 590 2001

Mesenchymal stem cells derived from bone marrow remyelinate demyelinated axons in the adult rat spinal cord.

Abst. Society for Neuroscience 2001

神経幹細胞応用の可能性について

脳神経外科 29 293 - 304 2001

T2 reversed fast spin-echo 画像と造影三次元脳表 MR angiography による脳動静脈奇形の画像診断

CI研究 23 165 - 175 2001

Mouse embryonic stem cells remyelinate demyelinated axons in the adult rat spinal cord. Abst.

Abst. Society for Neuroscience 2001

Transplantation of human neural stem cells repairs the ischemic lesions of the rat middle cerebral occlusion model.

Abst. Society for Neuroscience 2001

Clonal neural stem cells derived from adult human brain: Implication s for auto-transplantation therapy for CNS disease.

Restorative Neurology and Neuroscience. 17 147 - 147 2001

HONMOU Osamu, SASAKI Masanori, UEDE Teiji, HASHI Kazuo

Functional neurosurgery : proceedings of the annual meeting of the Japan Society for Stereotactic and Functional Neurosurgery 39 ( 2 ) 60 - 61 2000.12

Characteristic improvement of the function following schwann cell transplantation for demyelinated spinal cord

T Imaizumi, KL Lankford, JD Kocsis, O Honmou, Kohama, I, K Hashi

NEUROLOGICAL SURGERY 28 ( 8 ) 705 - 711 2000.08

Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord

T Kato, O Honmou, T Uede, K Hashi, JD Kocsis

GLIA 30 ( 3 ) 209 - 218 2000.05

Neural reconstruction by auto-transplantation of neural stem cells

HONMOU Osamu, FUKUI Masashi

Japanese journal of neurosurgery ( The Japanese Congress of Neurological Surgeons ) 9 ( 4 ) 290 - 290 2000.04

Excitability changes of dorsal root axons following nerve injury: implications for injury-induced changes in axonal Na+ channels

T Nonaka, O Honmou, J Sakai, K Hashi, JD Kocsis

BRAIN RESEARCH 859 ( 2 ) 280 - 285 2000.03

DNA diagnosis of PKD 1 gene in cerebral aneurysm patients.

Honmou Osamu, Akiyama Yukinori, Sasaki Masanori, Uede Teiji, Hashi Kazuo

Jpn. J. Stroke ( The Japan Stroke Society ) 22 ( 3 ) 457 - 461 2000

Polycystic kidney disease (PKD) is a genetic disorder characterized by the development of progressive cyst formation and enlargement in kidney. Cysts occur in the liver and other organs, and an association with various abnormalities of connective tissue has been reported, which changes include intracranial aneurysm, aortic dissection, and heart valve defects. Recently, the PKD 1 gene has been cloned and found to encode a 4303 amino acid protein, polycystin, which is thought to be involved in protein-protein and protein-carbohydrate interaction in the extracellular compartment. We have studied germline mutations in the PKD 1 gene by single-strand conformation polymorphism method and direct sequence analysis of genomic DNA from blood samples of 38 patients with cerebral aneurysms. In the present report, we demonstrate novel pathological mutations in two cerebral aneurysm patients who are not suffering from polycystic disease. These findings suggest PKD 1 mutation may play an important role in the development of cerebral aneurysm formation.

DOI CiNii

純粋語聾を呈したテント髄膜腫の１例

脳と神経 52 997 - 1001 2000

脳動脈瘤患者の遺伝子解析

脳循環代謝 12 271 - 272 2000

脊髄脱髄巣に移植された Schwann 細胞による機能回復の特徴

脳神経外科 28 705 - 11 2000

ヒト成熟脳由来神経幹細胞の神経細胞への機能的分化

新潟医学会雑誌 114 498 - 498 2000

脳機能再生を目指した基礎的研究の現状と展望

脳と循環 5 53 - 57 2000

Transplantation of clonal neural stem cells derived from adult human brain elicits functional repair of demyelinated spinal cod axons in the adult rat.

Restorative Neurology and Neuroscience. 16 15 - 15 2000

脳動脈瘤患者のPKD１遺伝子解析

脳血管攣縮 15 218 - 221 2000

B-15)ヒト成熟脳由来の神経幹細胞による神経移植療法（北日本脳神経外科連合会第23回学術集会）

本望修, 加藤孝顕, 秋山幸功, 上出廷治, 端和夫

新潟医学会雑誌 ( 新潟医学会 ) 113 ( 11 ) 564 - 564 1999.12

B-16)神経幹細胞を用いた自家移植療法に向けて : エコーガイドによる成熟サル大脳からの神経幹細胞の抽出・培養の試み（北日本脳神経外科連合会第23回学術集会）（北日本脳神経外科連合会第23回学術集会）

秋山幸功, 本望修, 加藤孝顕, 五十嵐幸治, 上出廷治, 端和夫

新潟医学会雑誌 ( 新潟医学会 ) 113 ( 11 ) 564 - 564 1999.12

B-14)中枢性脱髄疾患に対するヒト胎児神経幹細胞の移植（北日本脳神経外科連合会第23回学術集会）

五十嵐幸治, 本望修, 加藤孝顕, 秋山幸功, 上出廷治, 端和夫

新潟医学会雑誌 ( 新潟医学会 ) 113 ( 11 ) 563 - 564 1999.12

Schwann cell 異種移植によるCNS脱髄疾患治療—移植方法の検討—

神経外傷 22 110 - 115 1999

ヒト胎児脳由来神経幹細胞の神経外傷モデルへの移植

本望修

神経外傷 22 105 - 109 1999

脳動脈瘤患者の PKD1 遺伝子解析

脳血管攣縮 15 0-0 1999

The delayed depolarization in rat cutaneous afferent axons is reduced following nerve transection and ligation, but not crush: Implications for injury-induced axonal Na+ channel reorganization

J Sakai, O Honmou, JD Kocsis, K Hashi

MUSCLE & NERVE 21 ( 8 ) 1040 - 1047 1998.08

B-17)中枢神経系脱髄疾患への髄鞘形成細胞移植療法における免疫応答 : MHCノックアウトマウスを用いた主要組織適合抗原の検討（北日本脳神経外科連合会第22回学術集会）

加藤孝顕, 本望修, 酒井淳, 上出廷治, 端和夫

新潟医学会雑誌 ( 新潟医学会 ) 112 ( 8 ) 498 - 498 1998.08

B-16)神経損傷及び再生時のslow Na＾+ channel発現の制御（北日本脳神経外科連合会第22回学術集会）

野中雅, 本望修, 酒井淳, 端和夫

新潟医学会雑誌 ( 新潟医学会 ) 112 ( 8 ) 498 - 498 1998.08

B-18)神経幹細胞の脳および培養海馬への移植（北日本脳神経外科連合会第22回学術集会）

酒井淳, 本望修, 加藤孝顕, 端和夫

新潟医学会雑誌 ( 新潟医学会 ) 112 ( 8 ) 498 - 498 1998.08

B-19)てんかんに対する遺伝子療法（北日本脳神経外科連合会第22回学術集会）

本望修, 端和夫

新潟医学会雑誌 ( 新潟医学会 ) 112 ( 8 ) 498 - 499 1998.08

Transplantation of the genetically-engineering neural stem cell

HONMOU Osamu, KATO Takaaki, HASHI Kazuo

神経組織の成長・再生・移植 10 ( 1 ) 61 - 62 1998.06

Transplantation of the cultured human olfactory ensheathing cell to the rat demyelinated spinal cord

KATO Takaaki, HONMOU Osamu, HASHI Kazuo

神経組織の成長・再生・移植 10 ( 1 ) 23 - 24 1998.06

B-57)遺伝子組み換え細胞移植による脱髄疾患の治療 : 機能回復の評価と臨床応用への可能性(北日本脳神経外科連合会第21回学術集会)

DNA diagnosis in the NF2 gene

Tumor Research 32 33 - 39 1998

本望修, 端和夫

新潟医学会雑誌 ( 新潟医学会 ) 111 ( 9 ) 602 - 602 1997.09

B-56)神経損傷及び再生時におけるNa^+ channel発現の変化(北日本脳神経外科連合会第21回学術集会)

酒井淳, 本望修, 端和夫

新潟医学会雑誌 ( 新潟医学会 ) 111 ( 9 ) 602 - 602 1997.09