雌性生殖器官における成体幹細胞システムの解明と再生医学への応用

• 研究課題/領域番号: 14207066
• 研究種目: 基盤研究(A)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 産婦人科学
• 研究機関: 慶應義塾大学
• 研究代表者: 吉村 泰典 慶應義塾大学, 医学部, 教授 (10129736)
• 研究分担者: 岡野 栄之 慶應義塾大学, 医学部, 教授 (60160694) ; 丸山 哲夫 慶應義塾大学, 医学部, 講師 (10209702) ; 田中 守 慶應義塾大学, 医学部, 講師 (20207145) ; 松崎 有未 (伊谷 有未) 慶應義塾大学, 医学部, 助教授 (50338183) ; 内田 浩 慶應義塾大学, 医学部, 助手 (90286534) ; 清水 亜紀 慶應義塾大学, 医学部, 助手 (60306826)
• 研究期間 (年度): 2002 – 2004
• 研究課題ステータス: 完了 (2004年度)
• 配分額: 41,860千円 (直接経費: 32,200千円、間接経費: 9,660千円); 2004年度: 5,980千円 (直接経費: 4,600千円、間接経費: 1,380千円); 2003年度: 7,670千円 (直接経費: 5,900千円、間接経費: 1,770千円); 2002年度: 28,210千円 (直接経費: 21,700千円、間接経費: 6,510千円)
• キーワード: 子宮内膜 / 子宮平滑筋 / 幹細胞 / 分化 / 再生医学 / 子宮筋 / 免疫不全マウス / DNAマイクロアレイ

研究概要

本研究では、雌性生殖器官が有する様々な機能メカニズムを明らかにするために、その成体幹細胞の同定・分離・培養技術の確立を通じて、幹細胞システムの解明と再生医学への応用を目的とした。
1.雌性生殖器官における組織幹細胞の分離・同定および幹細胞特性の解明
a)子宮内膜の組織幹細胞
内膜はその高い再生能力から組織幹細胞の存在が強く示唆される。近年、組織幹細胞をside population細胞として分離する方法が開発された。月経周期を通して内膜にはSP(endometrial SP ; ESP)が存在し、免疫不全マウスへの移植実験では、ESP移植部位に腺管構造を有する内膜様組織が再構築され、加えて内膜組織の各コンポーネントより成る様々な組織も構築された。
b)子宮筋の組織幹細胞
子宮筋は妊娠・分娩時に著明な増大と細胞数の増加を示し、産褥期には急激にアポトーシスを起こす。そこで子宮平滑筋における組織幹細胞の同定と単離を目的として、ESP単離と同様の戦略に基づいて、ヒト正常子宮筋層から子宮筋SP(myometrial SP : MSP)を分離した。MSPは細胞周期上quiescentであり、in vitroで骨・脂肪細胞へ分化するとともに、in vivoでは平滑筋様の組織を構築した。
さらに、GeneChip解析によりESPやMSPの発現遺伝子群のなかにABCG2といった幹細胞マーカーが含まれていた。以上より、ESPやMSPが幹細胞的特性を有し、これらを中心とする幹細胞システムが雌性生殖器官に存在する可能性が示された。
2.内膜分化制御
分子標的という観点からヒストンアセチル化およびチロシンリン酸化経路を修飾する低分子化合物を用いたところ、短期間でかつ効率よく子宮内膜の分化を誘導し得た。内膜幹細胞の分化あるいは他の細胞系譜への細胞転換を行う上での基盤データが得られた。

研究成果

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• [雑誌論文] Non-hematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. (2004)
  • 著者名/発表者名: Kawada H, Fujita J, Kinjo K, Matsuzaki Y, Tsuma M, Miyatake H, Muguruma Y, Itabashi Y, Ikeda Y, Ogawa S, Okano H, Hotta T, Ando K, Fukuda K
  • 雑誌名: Blood 104 ページ: 3581-3587
• [雑誌論文] Retinoic acid-concentration-dependent acquisition of neural cell identity during in vitro differentiation of mouse embryonic stem cells. (2004)
  • 著者名/発表者名: Okada Y, Shimazaki T, Sobue G, Okano H
  • 雑誌名: Dev Biol 275 ページ: 124-142
• [雑誌論文] Differential expression of Pax6 and Ngn2 between pair-generated cortical neurons. (2004)
  • 著者名/発表者名: Kawaguchi A., Ogawa M., Saito K., Matsuzaki F., Okano H, Miyata T
  • 雑誌名: J Neurosci Res 78 ページ: 784-795
• [雑誌論文] Deltex induces an accumulation of the vesicular Notch protein and activates Suppressor of hairless-independent Notch signaling in Drosophila. (2004)
  • 著者名/発表者名: Hori K, Ito M., Fuwa TJ, Okano H., Baron M, Matsuno K
  • 雑誌名: Development 131 ページ: 5527-5537
• [雑誌論文] Comparison between fetal spinal cord-and forebrain-derived neural stem/progenitor cells as a source of transplantation for spinal cord injury (2004)
  • 著者名/発表者名: Watanabe K, Nakamura M, Iwanami A, Fujita Y, Kanemura Y, Toyama Y, Okano H
  • 雑誌名: Dev Neurosci 26 ページ: 275-287
  • NAID: 10014400968
• [雑誌論文] The origin of bone marrow-derived cardiomyocytes is mesenchymal : little contribution of hematopoietic cells. (2004)
  • 著者名/発表者名: Kawada H., Fujita J., Matsuzaki Y., Tsuma M., Miyatake H., Muguruma Y, Itabashi Y., Okano H., Ogawa S., Hotta T., Ando K., Fukuda K
  • 雑誌名: Blood (In press)
• [雑誌論文] Hematopoietic and nonhematopoietic potentials of Hoechst(low)/side population cells isolated from adult rat kidney. (2004)
  • 著者名/発表者名: Iwatani H, Ito T, Imai E, Matsuzaki Y, Suzuki A, Yamato M, Okabe M, Hori M
  • 雑誌名: Kidney Int 65 ページ: 1604-1614
• [雑誌論文] Insulin-like growth factors and their binding proteins : the potential relevance to reproductive physiology. (2003)
  • 著者名/発表者名: Yoshimura Y.
  • 雑誌名: Reprod Med Biol 2 ページ: 1-24
  • NAID: 10011370970
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Structure and expression of the human oocyte-specific histone H1 gene elucidated by direct RT-nested PCR of a single oocyte. (2003)
  • 著者名/発表者名: Tanaka Y, et al.
  • 雑誌名: Biochem Biophys Res Commun 304 ページ: 351-357
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Cutoff value of 1 h, 50 g glucose challenge test for screening of gestational diabetes mellitus in a Japanese population. (2003)
  • 著者名/発表者名: Miyakoshi K, et al.
  • 雑誌名: Diabetes Res Clin Pract 60 ページ: 63-67
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Reduced expression of αvβ3 integrin in the endometrium of patients with repearted IVF-ET failures : Improvement by danazol treatment. (2003)
  • 著者名/発表者名: Tei C, et al. :
  • 雑誌名: J Assist Reprod Fert 20 ページ: 13-20
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Involvement of histone acetylation in ovarian steroid-induced decidualization of human endometrial stromal cells. (2003)
  • 著者名/発表者名: Sakai N, et al.
  • 雑誌名: J Biol Chem 278 ページ: 16675-16682
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Expression of the exocytotic protein syntaxin in mouse oocytes. (2003)
  • 著者名/発表者名: Iwahashi K, et al.
  • 雑誌名: Reproduction 126 ページ: 73-81
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Checkmark fetal heart rate pattern associated with severe fatal hypoxia : A case report. (2003)
  • 著者名/発表者名: Kashiwagi S, et al.
  • 雑誌名: Fetal Diagn. Ther. 18 ページ: 237-239
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Oocyte maturation in humans : the potential relevance to reproductive medicine. (2003)
  • 著者名/発表者名: Yoshimura Y.
  • 雑誌名: J Mamm Ova Res 20 ページ: 86-92
  • NAID: 10012454974
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Fetal goitrous hypothyroidism followed by neonatal transient hypoerthyroidism. (2003)
  • 著者名/発表者名: Matsumoto T, et al.
  • 雑誌名: Fetal Diagn Ther 18 ページ: 459-462
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Electroporation of cynomolgus monkey embryonic stem cells. (2003)
  • 著者名/発表者名: Furuya M, et al.
  • 雑誌名: Genesis 37 ページ: 180-187
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Incidental deviation of short and long CAG repearts in the androgen receptor gene for Japanese male infertility. (2003)
  • 著者名/発表者名: Nakabayashi A, et al.
  • 雑誌名: Reprod Med Biol 2 ページ: 145-150
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Transplantation of meural stem cells into the spinal cord sfter injury. (2003)
  • 著者名/発表者名: Okano H, et al.
  • 雑誌名: Seminar in Cell & Developmental Biol 14 ページ: 191-198
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Insulin-like growth factors and their binding proteins : the potential relevance to reproductive physiology. (2003)
  • 著者名/発表者名: Yoshimura Y
  • 雑誌名: Reprod Med Biol 2 ページ: 1-24
  • NAID: 10011370970
  • 説明: 「研究成果報告書概要(欧文)」より
• [雑誌論文] Reduced expression of αvβ3 integrin in the endometrium of patients with repearted IVF-ET failures : Improvement by danazol treatment. (2003)
  • 著者名/発表者名: Tei C, et al.
  • 雑誌名: J Assist Reprod Fert 20 ページ: 13-20
  • 説明: 「研究成果報告書概要(欧文)」より
• [雑誌論文] Checkmark fetal heart rate pattern associated with severe fetal hypoxia : A case report. (2003)
  • 著者名/発表者名: Kashiwagi S, et al.
  • 雑誌名: Fetal Diagn.Ther. 18 ページ: 237-239
  • 説明: 「研究成果報告書概要(欧文)」より
• [雑誌論文] Oocyte maturation in humans : the potential relevance to reproductive medicine. (2003)
  • 著者名/発表者名: Yoshimura Y
  • 雑誌名: J Mamm Ova Res 20 ページ: 86-92
  • NAID: 10012454974
  • 説明: 「研究成果報告書概要(欧文)」より
• [雑誌論文] Transplantation of meural stem cells into the spinal cord sfter injury. (2003)
  • 著者名/発表者名: Okano H, et al.
  • 雑誌名: Seminar in Cell & Developmental Biol. 14 ページ: 191-198
  • 説明: 「研究成果報告書概要(欧文)」より
• [雑誌論文] Leydig cell-derived heme oxygenase-1 regulates apoptosis of premeiotic germ in response to stress. (2002)
  • 著者名/発表者名: Ozawa N, et al.
  • 雑誌名: J Clin Invest 109 ページ: 457-467
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Laparoscopic treatment of polycystic ovaries with the Holmium : YAG laser. (2002)
  • 著者名/発表者名: Asada H, et al.
  • 雑誌名: Fertil Steril 77 ページ: 852-853
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Protein tyrosine phosphorylation signaling in the differentiation of human endometrial stromal cells. (2002)
  • 著者名/発表者名: Maruyama T, et al.
  • 雑誌名: Keio J Med 51 ページ: 93-99
  • NAID: 50000574133
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] The role of integrins in the human reproductive process. (2002)
  • 著者名/発表者名: Yoshimura Y.
  • 雑誌名: J Reprod Dev 48 ページ: 215-232
  • NAID: 10026616395
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Oocyte-specific linker histone in mammalian species. (2002)
  • 著者名/発表者名: Tanaka M, et al.
  • 雑誌名: J Mamm Ova Res 19 ページ: 61-65
  • NAID: 130004436659
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Nonendothelial sources of nitric oxide in arterioles but in venules. Alternative source revealed in vivo by diaminofluorescein microfluorography. (2002)
  • 著者名/発表者名: Kashiwagi S, et al.
  • 雑誌名: Cir Res 91 ページ: 55-64
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Prenatal diagnosis of atelosteogenesis type I at 21 weeks' gestation. (2002)
  • 著者名/発表者名: Ueno K, et al.
  • 雑誌名: Prenat Diagn 22 ページ: 1071-1075
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Small guanosine triphospatase RhoA and Rho-associated kinase as regulators of trophoblast migration. (2002)
  • 著者名/発表者名: Shiokawa S, et al.
  • 雑誌名: J Clin Endocrinol Metab 87 ページ: 5808-5816
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Reactive oxygen species mediate leukocyte-endothelium interactions in prostaglandin F2α-induced luteolysis in rats. (2002)
  • 著者名/発表者名: Minegishi K, et al.
  • 雑誌名: Endocrinol Metab 283
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Expression and subcellular distribution of the active form of c-Src tyrosine kinase in differentiating human endometrial stromal cells. (2002)
  • 著者名/発表者名: Yamamoto Y, et al.
  • 雑誌名: Mol Hum Reprod 8 ページ: 1171-1124
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] A mammalian bromodomain protein Brd4 interacts with the replication factor C and inhibits progression to S phase. (2002)
  • 著者名/発表者名: Maruyama T, et al.
  • 雑誌名: Mol Cell Biol. 22 ページ: 6509-6520
  • 説明: 「研究成果報告書概要(和文)」より
• [雑誌論文] Laparoscopic treatment of polycystic ovaries with the Holmium: YAG laser. (2002)
  • 著者名/発表者名: Asada H, et al.
  • 雑誌名: Fertil Steril 77 ページ: 852-853
  • 説明: 「研究成果報告書概要(欧文)」より
• [雑誌論文] The role of integrins in the human reproductive process. (2002)
  • 著者名/発表者名: Yoshimura Y
  • 雑誌名: J Reprod Dev 48 ページ: 215-232
  • NAID: 10026616395
  • 説明: 「研究成果報告書概要(欧文)」より
• [雑誌論文] Nonendothelial source of nitric oxide in arterioles but not in venules. Alternative source revealed in vivo by diaminofluorescein microfluorography. (2002)
  • 著者名/発表者名: Kashiwagi S, et al.
  • 雑誌名: Cir Res 91
  • 説明: 「研究成果報告書概要(欧文)」より
• [雑誌論文] A mammalian bromodomain protein Brd4 interacts with the replication factor C and inhibits progression to S phase. (2002)
  • 著者名/発表者名: Maruyama T
  • 雑誌名: Mol Cell Biol. 22(18) ページ: 6509-6520
  • 説明: 「研究成果報告書概要(欧文)」より
• [産業財産権] 新規組織幹細胞 (2006)
  • 発明者名: 丸山哲夫,他
  • 権利者名: 慶應義塾
  • 産業財産権番号: 2006-022875
  • 出願年月日: 2006-01-31
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Maruvama T, Yamamoto Y, Shimizu A, Masuda H, Sakai N, Sakurai R, Asada H, Yoshimura Y: "Pyrazolo pyrimidine-type inhibitors of src family tyrosine kinases promote ovarian steroid-induced differentiation of human endometrial stromal cells In Vitro."Biol Reprod.. 70(1). 214-221 (2004)
• [文献書誌] Teranishi T, Tanaka M, Kimoto S, Ono Y, Miyakoshi K, Kono T, Yoshimura Y: "Rapid replacement of somatic linker histones with the oocyte-specific linker histone H1 foo in nuclear transfer."Dev Biol.. 266. 76-86 (2004)
• [文献書誌] Matsumoto T, Miyakoshi K, Kasai K, Ishimoto H, Tanaka M, Ikeda K, Yoshimura Y: "Fetal goitrous hypothyroidism followed by neonatal transient hypoerthyroidism."Fetal Diagn Ther.. 18. 459-462 (2003)
• [文献書誌] Yoshimura Y: "Oocyte maturation in humans : the potential relevance to reproductive medicine."J Mamm Ova Res.. 20. 86-92 (2003)
• [文献書誌] Kashiwagi S, Miyakoshi K, Ishimoto H, Tanaka M, Yoshimura Y: "Checkmark fetal heart rate pattern associated with severe fetal hypoxia : A case report."Fetal Diagn.Ther.. 18. 237-239 (2003)
• [文献書誌] Iwahashi K, Kuji N, Fujiwara T, Tanaka H, Takahashi J, Inagaki N, Komatsu S, Yamamoto A, Yoshimura Y, Akagawa K: "Expression of the exocytotic protein syntaxin in mouse oocytes."Reproduction.. 126. 73-81 (2003)
• [文献書誌] Sakai N, Maruyama T, Sakurai R, Masuda H, Yamamoto Y, Shimizu A, Kishi I, Asada H, Yamagoe S, Yoshimura Y: "Involvement of histone acetylation in ovarian steroid-induced decidualization of human endometrial stromal cells."J Biol Chem.. 278(19). 16675-16682 (2003)
• [文献書誌] Tei C, Maruyama T, Kuji N, Miyazaki T, Mikami M, Yoshimura Y: "Reduced expression of αvβ3 integrin in the endometrium of unexplained infertility patients with recurrent IVF-ET failures : Improvement by danazol treatment."J Assist Reprod Genet.. 20(1). 13-20 (2003)
• [文献書誌] Miyakoshi K, Tanaka M, Ueno K, Uehara K, Ishimoto H, Yoshimura Y: "Cutoff value of 1 h, 50 g glucose challenge test for screening of gestational diabetes mellitus in a Japanese population."Diabetes Res Clin Pract.. 60. 63-67 (2003)
• [文献書誌] Tanaka Y, Kato S, Tanaka M, Kuji N, Yoshimura Y: "Structure and expression of the human oocyte-specific histone H1 gene elucidated by direct RT-nested PCR of a single oocyte."Biochem Biophys Res Commun.. 304. 351-357 (2003)
• [文献書誌] Yoshimura Y: "Insulin-like growth factors and their binding proteins : the potential relevance to reproductive physiology."Reprod Med Biol.. 2. 1-24 (2003)
• [文献書誌] Ozawa Y, Nakao K, Takeda J, Akira S, Gruss P, Hirano T, Oguchi Y, Okano H: "Down-regulation of STAT3 activation is required as an intrinsic factor to complete rod photoreceptor differentiation."Mol.Cell.Neurosci.. (in press). (2004)
• [文献書誌] Mikami Y, Okano H, Sakaguchi M, Nakamura M, Shimazaki T, Okano HJ, Kawakami Y, Toyama Y, Toda M: "Implantation of dendritic cells in the injured adult spinal coed results in activation of the endogenous neural/progenitor cells for den novo neurogenesis and axonal regeneration, leading to functional recovery."J.Neurosci Res.. (in press). (2004)
• [文献書誌] Ohba H, Chiyoda T, Endo B, Yano M, Hayakawa Y, Sakaguchi M, Darnell RB, Okano HJ, Okano H: "Sox21 is a repressor of neuronal differentiation and is antagonized by YB-1."Neurosci.Lett.. (in press). (2004)
• [文献書誌] Watanabe K, Nakamura M, Iwanami A, Fujita Y, Kanemura Y, Toyama Y, Okano H: "Comparison between fetal spinal cord-and forebrain-derived neural stem/progenitor cells as a source of transplantation for spinal cord injury."Dev.Neurosci.. (in press). (2004)
• [文献書誌] Ieda M, Fukuda K, Kimura K, Hisaka Y, Kawaguchi H, Shimoda K, Takeshita E, Okano H, Kurihara Y, Kurihara H, Ishida J, Fukamizu A, Salamone L, Howard JF, Ogawa S: "Endothelin-1 regulates cardiac sympathetic nerve innervation in the rodent hearty by controlling nerve growth factor expression."J.Clini.Invest.. (in press). (2004)
• [文献書誌] Murata J, Murayama A, Horii A, Doi K, Harada T, Okano H, Kubo T: "Expression of Musashi1, a neural RNA-binding protein, in the cochler of young adult mice."Neuroscience Letter.. 354. 201-204 (2004)
• [文献書誌] Matsuzaki Y, Kinjo K, Mulligan RC, Okano H: "Unexpectedly efficient homing capacity of purified murine hematopoietic stem cell."Immunity.. 20. 87-93 (2004)
• [文献書誌] Yamashima T, Tonchev BA, Seki T, Sawamoto K, Okano H: "Vascular adventitia generates neuronal progenitors in monkey hippocampus after ischemia."Hippocampus.. (in press). (2004)
• [文献書誌] Okada S, Nakamura M, Mikami Y, Ohsugi Y, Yoshizaki K, Kishimoto T, Toyama Y, Okano H: "Blockade of interleukin-6 receptor ameliorates functional recovery in spinal cord injury."J.Neurosci Res.. (in press). (2004)
• [文献書誌] Hu QD, Ang BT, Karsak M, Hu WP, Cui XY, Duka T, Takeda Y, Chia W, Natesan S, Ng YK, Ling EA, Israel A, Maciag T, Small D, Trifonova R, Kopan R, Okano H, Nakafuku M, Chiba S, Hirai H, Schachner M, Pallen CJ, Watanabe K, Xiao ZC: "F3/Contactin acts as a functional ligand for Notch during oligodendrocyte maturation."Cell.. 115. 163-175 (2003)
• [文献書誌] Yoshida T, Tokunaga A, Nakao, Okano H: "Distinct expression patterns of splicing isoforms of mNumb in the endocrine lineage of developing pancreas."Differentiation.. 70. 486-495 (2003)
• [文献書誌] Miyanomori Y, Kobayashi H, Imai T, Watanabe M, Nagata T, Uesugi S, Okano H, Katahira M: "Origin of figher affinity to RNA of the N-terminal RNA-binding domain than that of the C-terminal one of a mouse neural protein, musashi1, as revealed by comparison of their structures, modes of interaction, surface electrostatic potentials, and backbone dynamics."J.Biol.Chem.. 278. 41309-41315 (2003)
• [文献書誌] Tamaki T, Akatsuka A, Okada, Y, Matsuzaki Y, Okano H, Kimura M: "Growth and differentiation potential of main- and side-population cells derived from murine skeletal muscle."Exp.Cell Res.. 291. 83-90 (2003)
• [文献書誌] Baker H, Kobayashi K, Okano H, Saino-Saito S: "Cortical and striatal expression of tyrosine hydroxylase mRNA in neonatal and adult mice."Cell Mol Neurobiol.. 23. 503-518 (2003)
• [文献書誌] Kanuka H, Kuranaga E, Hiratou T, Igaki T, Nelson B, Okano H, Miura M: "Cytosol-endoplasmic reticulum interplay by Sec61alpha translocon in polyglutamine-mediated neurotoxicity in Drosophila."Proc.Natl.Acad.Sci.USA.. 100. 11723-11728 (2003)
• [文献書誌] Ishizuya-Oka A, Shimizu K, Sakakibara SI, Okano H, Ueda S: "Thyroid hormone-upregulated expression of Musashi-1 is specific for progenitor cells of the adult epithelium during amphibian gastrointestinal remodeling."J Cell Sci.. 116. 3157-3164 (2003)
• [文献書誌] Kokuzawa J, Yoshimura S, Kitajima H, Shinoda J, Kaku Y, Iwama T, Morishita R, Shimazaki T, Okano H, Kunisada T, Sakai N: "Hepatocyte growth factor promotes proliferation and neural differentiation of neural stem cells from mouse embryos."Mol.Cell.Neurosci.. 24. 190-197 (2003)
• [文献書誌] Uchida K, Okano H, Hayashi T, Mine Y, Tanioka Y, Nomura T, Kawase T: "Grafted swine neuroepithelial stem cells can form myelinated axons and both efferent and afferent synapses with xenogeneic rat neurons."J.Neurosci.Res.. 72. 661-669 (2003)
• [文献書誌] Yuasa Y, Okabe M, Yoshikawa S, Tabuchi K, Xiong WC, Hiromi Y, Okano H: "Drosophila homeodomain protein REPO controls glial differentiation by cooperating with ETS and BTB transcription factors."Development.. 130. 2419-2428 (2003)
• [文献書誌] Nakamura Y, Yamamoto M, Oda E, Yamamoto A, Kanemura Y, Hara M, Suzuki A, Yamasaki M, Okano H: "Expression of tubulin beta II in neural stem/progenitor cells and radial fibers during human fetal brain development."Lab Invest.. 83. 479-489 (2003)
• [文献書誌] Sasaki T, Kitagawa K, Sugimura S, Omura-Matsuoka E, Tanaka S, Yagita Y, Okano H, Matsumoto M, Hori M: "Implication of Cyclooxygenase-2 on Enhanced Proliferation of Neural Progenitor Cells in the Adult Mouse Hippocampus After Ischemia."J.Neurosci.Res.. 72. 461-471 (2003)
• [文献書誌] Kayahara T, Sawada M, Takaishi S, Fukui H, Seno H, Fukuzawa H, Suzuki K, Hiai H, Kageyama R, Okano H, Chiba T: "Candidate markers for stem and early progenitor cells, Musashi-1 and Hes1, are expressed in crypt base columnar cells of mouse small intestine."FEBS Letter.. 535. 131-135 (2003)
• [文献書誌] Kuo H-C, Pau FKY, Yeoman RR, Mitalipov SM, Okano H, Wolf DP: "Differentiation of monkey embryonic stem cells into neural lineages."Biology of Reproduction.. 68. 1727-1735 (2003)
• [文献書誌] Tonchev AB, Yamashima T, Zhao L, Okano HJ, Okano H: "Proliferation of neural and neuronal progenitors after global brain ischemia in young adult macaque monkeys."Mol.Cell.Neurosci.. 23. 292-301 (2003)
• [文献書誌] Tonchev AB, Yamashima T, Zhao L, Okano H: "Differential proliferative response in the postischemic hippocampus, temporal cortex and olfactory bulb of adult primates."Glia.. 42. 209-224 (2003)
• [文献書誌] Potten CS, Booth C, Tudor GL, Booth D, Brady G, Hurley P, Ashton G, Clarke G, Sakakibara S, Okano H: "Identification of a putative intestinal stem cell marker and early lineage marker ; Musashi1."Differentiation. 71. 28-41 (2003)
• [文献書誌] Sakai N, Maruyama T, Sakurai R, Masuda H, Yamamoto Y, Shimizu A, Kishi I, Asada H, Yamagoe S. Yoshimura Y: "Involvement of histone acetylation in ovarian steroid-induced decidualization of human endometrial stromal cells"J Biol Chem. (in press). (2003)
• [文献書誌] Nakamura Y, Yamamoto M, Oda E, Yamamoto A, Kanemura Y, Hara M, Suzuki A, Yamasaki M, Okano H: "Experession of tubulin beta II in neural stem/progrenitor cells and radial fibers during human fetal brain development"Lab Invest. (in press). (2003)
• [文献書誌] Sasaki T, Kitagawa K, Sugimura S, Omura-Matsuoka E, Tanaka S. Yagita Y, Okano H, Matsumoto M, Hori M: "Implication of Cyclooxygenase-2 on enhanced neurogenesis in the adult hippocampus after ischemia"J. Neurosci. Res. (in press). (2003)
• [文献書誌] Okano H, Ogawa Y, Nakamura M, Kaneko S, Iwanami A, Toyama A: "Transplantation of neural stem cells into the spinal cord after injury"Seminar in Cell & Devlopmental Biol. (in press). (2003)
• [文献書誌] Yoshimura Y: "Insulin-like growth factors and their binding proteins: the potential relevance to reproductive physiology"Reprod Med Biol. 2. 11-34 (2003)
• [文献書誌] Ozawa N, Goda N, Makino N, Yamaguchi T, Yoshimura Y, Suematsu M: "Leydig cell-derived heme oxygenase-1 regulates apoptosis of premeiotic germ in response to stress"J Clin Invest. 109. 457-467 (2002)
• [文献書誌] Tei C, Maruyama T, Kuji N, Miyazaki T, Mikami M, Yoshimura Y: "Reduced expression of avb3 integrin in the endometrium of unexplained infertility patients with recurrent IVF-ET failures: Improvement by danazol treatment"J Assist Reprod Genet. 20(1). 13-20 (2003)
• [文献書誌] Maruyama T, Farina A, Dey A, Cheong J, Bermudez VP, Tamura T, Sciortino S, Shuman J, Hurwitz J, Ozato K: "A mammalian bromodomain protein Brd4 interacts with the replication factor C and inhibits progression to S phase"Mol Cell Biol. 22(18). 6509-6520 (2002)
• [文献書誌] Yamamoto Y, Maruyama T, Sakai N, Sakurai R, Shimizu A, Hamatani T, Uchida H, Sabe H. Yoshimura Y: "Expression and subcellular distribution of the active form of c-Src tyrosine kinase in differentiating human endometrial stromal cells"Mol Hum Reprod. 8(12). 1117-1124 (2002)
• [文献書誌] Asada H, Kishi I, Kaseda S, Nakagawa H, Maruyama T, Yoshimura Y: "Laparoscopic treatment of polycystic ovaries with the Holmium: YAG laser"Fertil Steril. 4(77). 852-853 (2002)
• [文献書誌] Minegishi K, Tanaka M, Nishimura O, Tanigaki S, Miyakoshi K, Ishimoto H, Yoshimura Y: "Reactive oxygen species mediate leukocyte-endothelium interactions in prostaglandin F 2α -induced luteolysis in rats"Am J Physiol Endocrinol Metad. 283. E1308-E1315 (2002)
• [文献書誌] Shiokawa S, Iwashita M, Akimoto Y, Nagamathu S, Sakai K, Hamashi H, Kabir-Salmani M, Nakamura Y, Uehata M, Yoshimura Y: "Small guanosine triphospatase RhoA and Rho-associated kinase as regulators of trophoblast migration"J Clin Endocrinol Metab. 87. 5808-5816 (2002)
• [文献書誌] Ueno K, Tanaka M, Miyakoshi K, Zhao C, Shinmoto H, Nishimura G, Yoshimura Y: "Prenatal diagnosis of atelosteogenesis type I at 21 weeks' gestation"Prenat Diagn. 22. 1071-1075 (2002)
• [文献書誌] Kashiwagi S, Kajimura M, Yoshimura Y, Suemathu M: "Nonendothelial source of nitric oxide in arterioles but not in venules. Alternative source revealed in vivo by diaminofluorescein microfluorogrphy"Cir Res. 91. e55-e64 (2002)
• [文献書誌] Tanaka M, Teranishi T, Miyakoshi K, Jiaxue W, Ueno K, Mathumoto T, Hattori Y, Yoshimura Y: "Oocyte-specific linker histone in mammalian species"J Mamm Ova Res. 19. 60-65 (2002)
• [文献書誌] Yoshimura Y: "The role of integrins in the human reproductive process"J Reprod Dev. 48. 215-232 (2002)
• [文献書誌] Maruyama T, Yamamoto Y, Sakai N, Shimizu A, Shimoki A, Masuda H, Yoshimura Y: "Protein tyrosine phosphorylation signaling in the differentiation of human endmetrial stromal cells"Keio J Med. 6(51). 93-99 (2002)
• [文献書誌] Ozawa N, Goda N, Makino N, Yamaguchi T, Yoshimura Y, Suematsu M: "Leydig cell-derived heme oxygenase-1 regulates apoptosis of premeiotic germ in response to stress"J Clin Invest. 109. 457-467 (2002)
• [文献書誌] Sakakibara S, Nakamura Y, Koike M, Takano H, Uchiyama, Noda T, Okano H: "RNA-binding protein Musashi family, roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation"Proc Natl Acad Sci USA. 99. 15194-15199 (2002)
• [文献書誌] Kuranaga E, Kanuka H, Igaki T, Sawamoto K, Ichijo H, Okano H, Miura M: "Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila"Nature Cell Biol. 4. 705-710 (2002)
• [文献書誌] Kanemura Y, Mon H, Kobayashi S, Islam O, Kodama E, Yamamoto A, Nakanishi Y, Arita N, Yamasaki M, Okano H, Miyake J, Hara M: "Evaluation of in-vitro proliferative activity of human fetal neural stem cell"J Neurosci Res. 69. 869-879 (2002)
• [文献書誌] Johansson CB, Lothian C, Molin M, Okano H, Lendahi U: "Nestin enhancer requirements for expression in normal and injured adult CNS"J. Neurosci Res. 69. 784-794 (2002)
• [文献書誌] Murayama A, Matsuzaki Y, Kawaguti A, Shimazaki T, Okano H: "Flow cytometric analysis of stem cells in the developing and adult mouse brain"J Neurosci Res. 69. 837-847 (2002)
• [文献書誌] Ogawa Y, Sawamoto K, Miyata T, Miyao S, Watanabe M, Toyama Y, Nakamura M, Bregman B.S, Koike M, Uchiyama Y, Okano H: "Transplantation of in vitro expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats"J Neurosci Res. 69. 925-953 (2002)
• [文献書誌] Yagita Y, Kitagawa K, Sasaki T, Miyata T, Okano H, Hori T, Matsumoto M: "Musashi1 and Nestin as useful markers of neuronal progenitor cells in rat hippocampus after forebrain ischemia"J Neurosci Res. 69. 750-756 (2002)
• [文献書誌] Shamloula H.K, Mbogho M.P, Pimentel A.C, Chrzanowska-Lightowlers Z.M.A, Hyatt V, Okano H.Venkatech T.R: "rugose (rg), a Drosophila A kinase Anchor Protein (DAKAP), is required for required for retinal pattern formation and interacts genetically with multiple signaling pathways"Genetics. 161. 693-710 (2002)
• [文献書誌] Cuadrado A, Garcia-Fernandez L.F, Imai T, Okano H, Munoz A: "Neural RNA-binding protein Musashi-1 modulates tau pre-mRNA alternative splicing and is regulated by thyroid hormone in the developing rat brain"Mol Cell Neurosci. 20. 198-210 (2002)
• [文献書誌] Shu H-J, Saito T, Watanabe H, Ito J-I, Takeda H, Okano H, Kawata S: "Expression of the Musashil gene encoding the RNA-binding protein in human hepatoma cell lines"Biochem Biophys Res Com. 293. 150-154 (2002)
• [文献書誌] Shibata M, Yamawaki T, Sasaki T, Hattori H, Hamada J, Fukuuchi Y, Okano H, Miura M: "Upregulation of Akt phosphorylation at the early stage of middle cerebral artery occlusion in mice"Brain Res. 942. 1-10 (2002)
• [文献書誌] Iwai Y, Hirota Y, Ozaki K, Okano H, Takeichi M, Uemura T: "DN-cadherin-dependent synaptogenesis in the Drosophila visual system"Mol Cell Neurosci. 19. 375-388 (2002)
• [文献書誌] Takasawa K.-I, Kitagawa K, Yagita Y, Sasaki T, Tanaka S, Ohtsuki T, Miyata T, Okano H, Hori M, Matsumoto M: "Increased proliferation of neural progenitor cells but reduced survival newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats"J Cereb Blood Flow Metab. 22. 299-307 (2002)
• [文献書誌] Okano H: "Neural stem cells: progression of basic research and perspective for clinical application"Keio J Med. 51. 115-158 (2002)
• [文献書誌] Okano H: "The stem cell biology of the central nervous system"J Neurosci Res. 69. 698-707 (2002)
• [文献書誌] Okano H, Imai T, Okabe M: "Musashi: a translational regulator of cell fates"J Cell Sci. 115. 1355-1359 (2002)
• [文献書誌] Okano H, Yoshizaki I, Shimazaki T, Sawamoto K: "Isolation and transplantation of dopaminergic neurons and neural stem cells"Parkinsonism Relat Disord. 9. 23-28 (2002)
• [文献書誌] Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA.: "" Stemness" : transcriptional profiling of embryonic and adult stem cells"Science. 298(5593). 597-600 (2002)
• [文献書誌] 丸山哲夫, 吉村泰典: "「臨床エビデンス婦人科学」生殖内分泌疾患[総論]ホルモン療法の基本"メジカルビュー(in press). (2003)
• [文献書誌] 鈴森 薫, 吉村 泰典, 堤 治 編: "新しい産科学.生殖医療から周産期医療まで"名古屋大学出版会. 286 (2002)
• [文献書誌] 吉村 泰典: "生殖医療のあり方を問う"診断と治療社. 156 (2002)
• [文献書誌] 吉村 泰典 編: "インフォームドコンセントのための図説シリーズ子宮内膜症"医薬ジャーナル社. 44 (2002)