成体幹細胞を用いた雌性生殖器官の臓器再生と疾患モデルの構築

2007 Fiscal Year Annual Research Report

• Project/Area Number: 17209053
• Research Institution: Keio University
• Principal Investigator: 吉村 泰典 Keio University, 医学部, 教授 (10129736)
• Co-Investigator(Kenkyū-buntansha): 丸山 哲夫 慶應義塾大学, 医学部, 講師 (10209702) ; 内田 浩 慶應義塾大学, 医学部, 助教 (90286534) ; 松崎 有未 慶應義塾大学, 医学部, 准教授 (50338183) ; 梶谷 宇 慶應義塾大学, 医学部, 助教 (60407111)
• Keywords: 子宮内膜 / 子宮筋 / 幹細胞 / 免疫不全マウス / 再生

Research Abstract

これまで、子宮内膜のSP分画に内膜幹細胞が濃縮されていることを明らかにしたが、今年度は、さらにSP分画のなかでCD31+/CD45-細胞が、少なくともin vitroにおいては、内膜間質細胞、血管内皮細胞、および血管平滑筋細胞に分化し得る能力を有することを明らかにした(論文準備中)。現時点では、内膜を構成する重要なコンポーネントである腺上皮細胞に分化する細胞集団を、SP分画から同定・単離するには至っていない。
子宮筋については、幾つかの表面マーカーを組み合わせることにより、SP法に依らない新しい方法で子宮筋幹細胞を分離することに成功した。すなわち、この分画はSP細胞を多く含み、SP法で単離した幹細胞集団と同様、1.低酸案下で好んで増殖する、2.脂肪、骨、軟骨への分化能力(多分化能)を有する、3.重度免疫不全マウスの子宮において、ヒト子宮筋を構築する、といった子宮筋幹細胞の要件を満たすことが判明した(論文準備中)。
内膜細胞あるいはその幹細胞から胚受容能を有するヒト内膜組織を再構築しin vitro着床システムの確立を目指しているが、その実験ツールとして、ヒト絨毛細胞株スフェロイド(胚に相当)と内膜腺上皮株を用いたin vitro着床モデルを確立した(Uchida, et. al.,Hum Reprod,2007)。また、着床には内股分化が必須だが、その分化を担う分子メカニズムを明らかにし、それを標的にした着床制御に必要な基盤データも得た(Uchida, et. al.,Endocrinology,2007;Nagashima, et. al.,Endocrinology,2008)。

Research Products

• [Journal Article] Clinical significance of parental chromosome rearrangements in the management of repeated pregnancy loss. (2008)
  • Author(s): Ozawa N, Maruyama T, Nagashima T, Ono M, Arase T, Ishimoto H, Yoshimura Y
  • Journal Title: Fertility and Sterility (In press)
  • Peer Reviewed
• [Journal Article] Occipital hemangioma:prenatal sonographic and magnetic resonance image. (2008)
  • Author(s): Miyakoshi K, Tanaka M, Matsumoto T, Hattori Y, Minegishi K, Ishimoto H, Yoshimura Y
  • Journal Title: J Obstet Gynecol Res (In press)
  • Peer Reviewed
• [Journal Article] Histone deacetylase inhibitors stimulate cell migration in human endometrial adenocarcinoma cells through up-regulation of glycodelin. (2007)
  • Author(s): Uchida H, Maruyama T, Ono M, Ohta K, Kajitani T, Masuda H, TNagashima T, Arase T, Asada H, Yoshimura Y
  • Journal Title: Endocrinology 148 Pages: 896-902
  • Peer Reviewed
• [Journal Article] Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/gammacnull immunodeficient mice. (2007)
  • Author(s): Masuda H, Maruyama T, Hiratsu E, Yamane J, Iwanami A, Nagashima T, Ono M, Miyoshi H, Okano HJ, Ito M, Tamaoki N, Nomura T, Okano H, Matsuzaki Y, Yoshimura Y
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 1925-1930
  • Peer Reviewed
• [Journal Article] Histone acetylation and subcellular localization of chromosomal protein BRD4 during mouse oocyte meiosis and mitosis. (2007)
  • Author(s): Nagashima T, Maruyama T, Furuya M, Kajitani T, Uchida H, Masuda H, Ono M, Arase T, Ozato K, Yoshimura Y
  • Journal Title: Mol Hum Reprod 13 Pages: 141-148
  • Peer Reviewed
• [Journal Article] Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities. (2007)
  • Author(s): Watanabe M, Yoshida R, Ueoka K, Aoki K, Sasagawa I, Hasegawa T, Sueoka K, Kamatani N, Ybshimura Y, Ogata T
  • Journal Title: Hum Reprod 22 Pages: 1279-1284
  • Peer Reviewed
• [Journal Article] 'Working'cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells. (2007)
  • Author(s): Okamoto K, Miyoshi S, Toyoda M, Hida N, Ikegami Y, Makino H, Nishiyama N, Tsuji H, Cui CH, Segawa K, Uyama T, Kami D, Miyado K, Asada H, Matsumoto K, Saito H, Yoshimura Y, Ogawa S, Aeba R, Yozu R, Umezawa A
  • Journal Title: Exp Cell Res 313 Pages: 2550-2562
  • Peer Reviewed
• [Journal Article] 1 (2007)
  • Author(s): Furuya M, Tanaka M, Teranishi T, Matsumoto K, Hosoi Y, Saeki K, Ishimoto H, Minegishi K, Iritani A, Yoshimura Y
  • Journal Title: J Reprod Dev 53 Pages: 895-902
  • Peer Reviewed
• [Journal Article] Elimination of HIV-1from semen and application of the processed semen to assisted reproductive technology. (2007)
  • Author(s): Kuji N, Mizusawa Y, Naganishi M, Hamatani T, Iwata S, Yoshimura Y
  • Journal Title: Reprod Med Biol 6 Pages: 151-156
• [Journal Article] The development of novel quantification assay for mitochondrial DNA heteroplasmy aimed at preimplantation genetic diagnosis of Leigh encephalopathy. (2007)
  • Author(s): Tajima H, Sueoka K, Moon SY, Nakabayashi A, Sakurai T, Murakoshi Y, Watanabe H, Iwata S, Hashiba T, Kato S, Goto YI, Ybshimura Y
  • Journal Title: J Assist Reprod Genet 24 Pages: 227-232
  • Peer Reviewed
• [Journal Article] Well-devised quantification analysis for duplication mutation of Duchenne muscular dystrophy aimed at preimplantation genetic diagnosis. (2007)
  • Author(s): Nakabayashi A, Sueoka K, Tajima H, Sato K, Sakamoto Y, Katou S, Yoshimura Y
  • Journal Title: J Assist Reprod Genet 24 Pages: 233-240
  • Peer Reviewed
• [Journal Article] Side population in human uterine myometrium displays phynotypic and functional characteristics of myometrial stem cells. (2007)
  • Author(s): Ono M, Maruyama T, Masuda H, Kajitani T, Nagashima T, Arase T, Ito M, Ohta K, Uchida H, Asada H, Yoshimura Y, Okano H, Matsuzaki Y
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 18700-18705
  • Peer Reviewed
• [Journal Article] Human amniotic membrane-derived stem cell with lack of Hla-dr expression can be a promising cellular source for cardiac stem cell therapy. (2007)
  • Author(s): Ikegami Y, Tsuji H, Miyoshi S, Hida N, Asada H, Uyama T, Umezawa A, Yoshimura Y, Ogawa S
  • Journal Title: J Am Coll cardiol 49 Pages: 47A
  • Peer Reviewed
• [Journal Article] Histone deacetylase inhibitor-induced glycodelin enhances the initial step of implantation. (2007)
  • Author(s): Uchida H^*, Maruyama T, Ohta K, Ono M, Arase T, Kagami M, Oda H, Kajitani T, Asada H, Toshimura Y
  • Journal Title: Human Reproduction 22 Pages: 2615-2622
  • Peer Reviewed
• [Journal Article] Analysis of serum FSH bioactivity in a patient with an FSH-secreting pituitary microadenoma and multicystic ovaries:ACase report. (2007)
  • Author(s): Kajitani T, Shunyu L, Maruyama T, Uchida H, Sakurai R, Masuda H, Nagashima T, Ono M, Arase T, Yoshimura Y
  • Journal Title: Hum Reprod 23 Pages: 435-439
  • Peer Reviewed