Cardiomyogenesis and the Mechanism of Immunologic Tolerance of Human Amniotic Mesenchymal Stem Cell

• Project/Area Number: 20791175
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: NISHIYAMA Hiroko National Research Institute for Child Health and Development, 生殖・細胞医療研究部, 共同研究員 (70383891)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 生科学 / 生殖医療 / 羊膜幹細胞 / バイオマテリアル

Research Abstract

Mesenchymal stem cells (MSCs) have recently been used for clinical application, and their safety and feasibility in cardiac stem cell-based therapy have been demonstrated, specially human bone marrow-derived MSCs (BMMSCs). Thus, MSCs are a more important cellular source for stem cell-based therapy from a practical point of view. However there are several problems. The efficacy of BMMSCs was still limited, however, because of low efficiency for cardiomyogenic transdifferentiation. The establishment of stem cell bank system and the use of immunosuppressant agents were also essential. While human amniotic membrane-derived mesenchymal stem cells (hAMCs) is known to differentiate into many tissues in vitro. Moreover human amniotic membrane is thought to play an important role for immunologic tolerance during pregnancy with expression of HLA-G, the non-classical human lerukocyte antigen (HLA) class I b. In the present study, we aimed to show hAMCs has a potency of cardiomyocyte differentiation, transplanted hAMCs-induced immunological tolerance and survival of transdifferentiated cardiomyocyte from HAMC in vivo.

Research Products

• [Journal Article] Dystrophin conferral using human endothelium expressing HLA-E in the non-immunosuppressive murine model of Duchenne muscular dystrophy. (2011)
  • Author(s): Cui CH, Miyoshi S, Tsuji H, Makino H, Kanzaki S, Kami D, Terai M, Suzuki H, Umezawa A.
  • Journal Title: Hum Mol Genet.(Epub 2010 Oct 14.) 20(2) Pages: 235-244
• [Journal Article] Pretreatment of Human Mesenchymal Stem Cells with Pioglitazone Improved Efficiency of Cardiomyogenic Transdifferentiation and Improved Cardiac Function. (2010)
  • Author(s): Shinmura D, Togashi I, Miyoshi S, Nishiyama N, Hida N, Tsuji H, Tsuruta H, Nakamizo H, Segawa K, Tsukada Y, Ogawa S, Umezawa A.
  • Journal Title: Stem Cells.(Epub ahead of print)
• [Journal Article] Xenografted human amniotic membrane-derived mesenchymal stem cells are immunologically tolerated and transdifferentiated into cardiomyocytes. (2010)
  • Author(s): Tsuji H, Miyoshi S, Ikegami Y, Hida N, Asada H, Togashi I, Suzuki J, Satake M, Nakamizo H, Tanaka M, Mori T, Segawa K, Nishiyama N, Inoue J, Makino H, Miyado K, Ogawa S, Yoshimura Y, Umezawa A.
  • Journal Title: Circ Res. 106(10) Pages: 1613-1623
• [Journal Article] Xenografted Human Amniotic Membrane-Derived Mesenchymal Stem Cells were Immunologically Tolerated and Transdifferentiated Into Cardiomyocytes (2010)
  • Author(s): Hiroko Tsuji, Shunichiro Miyoshi, Yukinori Ikegami, Naoko Hida, Hironori Asada, Ikuko Togashi, Junshi Suzuki, Masaki Satake, Hikaru Nakamizo, Mamoru Tanaka, Taisuke Mori, Kaoru Segawa, Nobuhiro Nishiyama, Junko Inoue, Hatsune Makino, Kenji Miyado, Satoshi Ogawa, Yasunori Yoshimura, Akihiro Umezawa.
  • Journal Title: Circulation Research Volume: 106(10) Pages: 1613-1623
  • Peer Reviewed
• [Journal Article] 子宮内膜症の発症に対して、EP300遺伝子多型が及ぼす影響 (2009)
  • Author(s): 辻紘子, 浅田弘法, 浅井哲, 古谷正敬, 内田 浩, 浜谷敏生, 丸山哲夫, 小崎健次郎, 柳橋達彦, 羽田智則, 安藤正明, 田島敏秀, 木挽貢慈, 吉村泰典
  • Journal Title: 日本エンドメトリオーシス学会会誌 30 Pages: 110-111
• [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 C H, 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(12) Pages: 2550-2562
• [Journal Article] ヒト子宮内膜由来間質細胞の心筋へのin situ分化転換(In Situ Cardiomyogenic Transdifferentiation Potential of Human Uterine Endometrium-derived Mesenchymal Cell) : NishiyamaNobuhiro(慶應義塾大学 循環器科) (2007)
  • Author(s): Miyoshi S, Hida N, Ikegami Y, Okamoto K, Uyama T, Shimizu T, Miyado K, Segawa K, Tsuji H, Okano T, Sakamoto M, Umezawa A, Ogawa S
  • Journal Title: Circulation Journal (1346-9843) 71巻Suppl.I Pages: 299-299
• [Journal Article] HLA-DRを発現しないヒト羊膜由来幹細胞は心臓幹細胞治療の有望な細胞源となる(Human Amniotic Membrane-derived Stem Cell with no HLA-DR Expression can be a Promising Cellular Source for Cardiac Stem Cell Therapy) : Ikegami Y (慶應義塾大学循環器内科) (2007)
  • Author(s): Tsuji H, Miyoshi S, Hida N, Asada H, Uyama T, Umezawa A, Yoshimura Y, Ogawa S
  • Journal Title: Circulation Journal (1346-9843) 71巻 Pages: 177-177
• [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 A, Ogawa S
  • Journal Title: Journal of the American College of Cardiology 49(9)
• [Journal Article] In Situ Cardiomyogenic Transdifferentiation Potential Of Human Uterine Endometrium-derived Mesenchymal Cell. (2007)
  • Author(s): Nishiyama N, Miyoshi S, Hida N, Ikegami Y, Okamoto K, Uyama T, Shimizu T, Miyado K, Segawa K, Kiyono T, Kyo S, Tsuji H, Okano T, Sakamoto M, Umezawa A, Ogawa S
  • Journal Title: Journal of the American College of Cardiology 49(9)
• [Journal Article] Human Menstrual Blood-Derived Mesenchymal Stem Cell Can Restore Impaired Cardiac Function By Cardiomyogenesis In Vivo. (2007)
  • Author(s): Miyoshi S, Kira S, Nishiyama N, Hida N, Mori T, Ikegami Y, Okamoto K, Uyama T, Cui C H, Miyado K, Uchiyama M, Segawa K, Tsuji H, Sakamoto M, Umezawa A, Ogawa S
  • Journal Title: Journal of the American College of Cardiology 49(9)
• [Journal Article] 帝王切開後に発症した急性結腸偽閉塞症(Ogilvie症候群)の一例:辻紘子(国立病院機構栃木病院産婦人科) (2006)
  • Author(s): 西村修, 鶴田智彦, 舛本暢生, 菊地正晃
  • Journal Title: 栃木県産婦人科医報 32巻2号 Pages: 169-172
• [Journal Article] 先天性サイトメガロウイルス感染症の一症例:西村修(国立病院機構栃木病院産婦人科) (2006)
  • Author(s): 辻紘子, 舛本暢生, 菊地正晃, 山口禎夫, 桑島成子
  • Journal Title: 栃木県産婦人科医報 32巻2号 Pages: 165-168
• [Journal Article] 卵巣類内膜腺癌Sertoliform variantの1例:辻紘子(国立病院機構埼玉病院 産婦人科) (2005)
  • Author(s): 小宮山慎一, 桑原佳子, 石川光也, 田中京子, 島田志保, 三上幹男
  • Journal Title: 日本産科婦人科学会埼玉地方部会会誌(0911-6281) 35巻 Pages: 80-85
• [Journal Article] 帝王切開後に発生したOgilvie症候群(急性結腸偽閉塞症)の2症例:鶴田智彦(国立病院機構栃木病院 産婦人科) (2005)
  • Author(s): 西村修, 辻紘子, 舛本暢生, 菊地正晃
  • Journal Title: 日本産科婦人科学会関東連合地方部会会報(0285-8096) 42巻3号 Pages: 345-345
• [Journal Article] 再発卵巣癌に対するgemcitabineの使用経験:辻紘子(国立病院機構埼玉病院産婦人科) (2005)
  • Author(s): 小宮山慎一, 村上功, 仲村勝, 倉橋崇, 田中京子, 鄭智誠, 三上幹男
  • Journal Title: 日本産科婦人科学会関東連合地方部会会報(0285-8096) 42巻2号 Pages: 216-216
• [Journal Article] 非典型的な進展形式を示し,診断に苦慮した卵管癌の1例:浅井哲(国立病院機構埼玉病院 産婦人科) (2004)
  • Author(s): 小宮山慎一, 土光順子, 辻紘子, 桑原佳子, 石川光也, 田中京子, 小南公人, 三上幹男
  • Journal Title: 日本産科婦人科学会埼玉地方部会会誌(0911-6281) 34巻 Pages: 3-7
• [Journal Article] 術前の腫瘍マーカーCA546の値は卵巣漿液性腺癌の予後を推定する因子となりうる:辻紘子(慶應義塾大学産婦人科) (2004)
  • Author(s): 青木大輔, 野村弘行, 鈴木直, 富田明代, 平尾健, 江澤佐知子, 玉田裕, 鈴木淳, 進伸幸, 吉村泰典, 野澤志朗
  • Journal Title: 日本産科婦人科学会関東連合地方部会会報(0285-8096) 41巻3号 Pages: 249-249
• [Journal Article] 子宮腺筋症から発生したと考えられる子宮癌肉腫の一例:桑原佳子(国立埼玉病院産婦人科) (2004)
  • Author(s): 辻紘子, 石川光也, 田中京子, 小宮山慎一, 廣瀬隆則, 三上幹男
  • Journal Title: 日本臨床細胞学会雑誌(0387-1193) 43巻Suppl.1 Pages: 243-243
• [Journal Article] 卵巣甲状腺腫性カルチノイドの一例:辻紘子(国立埼玉病院産婦人科) (2004)
  • Author(s): 小宮山慎一, 桑原佳子, 石川光也, 田中京子, 三上幹男
  • Journal Title: 日本産科婦人科学会関東連合地方部会会報(0285-8096) 41巻2号 Pages: 153-153
• [Presentation] 女性医師にとっての腹腔鏡下手術の問題点 (2010)
  • Author(s): 辻紘子、伊藤嘉佑子、古谷正敬、浅田弘法、吉村泰典、木挽貢慈
  • Organizer: 第23回に本内視鏡外科学会
  • Year and Date: 2010-10-20
• [Presentation] Xenografted Human Amniotic Membrane-Derived Mesenchymal Stem Cells were Immunologically Tolerated and Transdifferentiated Into Cardiomyocytes (2010)
  • Author(s): 辻紘子
  • Organizer: 第18回日本胎盤学会
  • Year and Date: 2010-10-01
• [Presentation] Xenografted Human Amniotic Membrane-Derived Mesenchymal Stem Cells are Immunologically Tolerated and Transdifferentiated Into Cardiomyocytes(ヒト羊膜由来間葉系幹細胞は、異種移植下で免疫学的寛容が成立し心筋に分化する) (2010)
  • Author(s): 辻紘子
  • Organizer: 第18回日本胎盤学会 学術集会 第28回日本絨毛性疾患研究会 学術集会
  • Place of Presentation: ホテル日航熊本
  • Year and Date: 2010-10-01
• [Presentation] 腹腔鏡下にて治療可能であった卵管間質部妊娠の3例 (2010)
  • Author(s): 辻紘子、伊藤嘉佑子、古谷正敬、内田浩、浜谷敏生、浅田弘法、丸山哲夫、久慈直昭、末岡浩、吉村泰典
  • Organizer: 第50回日本産科婦人科内視鏡学会
  • Year and Date: 2010-07-30
• [Presentation] Pretreatement with IL10 significantly improved efficiency of immunological tolerance and rate of survival of cardiomyocyte transdifferentiated from human amniotic membrane-derived mesenchymal stem cell in vivo. (2010)
  • Author(s): Hiroko Tsuji, Shunichiro Miyoshi, Naoko Hida, Nobuhiro Nishiyama, Ikuko Togashi, Hikaru Nakamizo, Yukinori Ikegai, Kaoru Segawa, Yasunori Yoshimura, Satoshi Ogawa, Akihiro Umezawa.
  • Organizer: 第74回日本循環器学会
  • Year and Date: 2010-03-07
• [Presentation] Pretreatement with IL10 significantly itnproved efficiency of immunological tolerance and rate of survival of cardiomyocyte transdifferentiated from human amniotic membrane-derived mesenchymal stem cell in vivo. (2010)
  • Author(s): Hiroko Tsuji, Shunichiro Miyoshi, Naoko Hida, Nobuhiro Nishiyama, Ikuko Togashi, Hikaru Nakamizo, Yukinori Ikegai, Kaoru Segawa, Yasunori Yoshimura, Satoshi Ogawa, Akihiro Umezawa
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2010-03-06
• [Presentation] 子宮内膜症の発症に対して、EP300およびAHRR遺伝子多型がおよぼす影響 (2009)
  • Author(s): 辻紘子、浅田弘法、浅井哲、古谷正敬、内田浩、浜谷敏生、丸山哲夫、小崎健次郎、柳橋達彦、羽田智則、安藤正明、木挽貢慈、吉村泰典
  • Organizer: 第30回日本エンドメトリオーシス学会
  • Year and Date: 2009-01-17
• [Presentation] Xenografted human amniotic membrane-derived mesenchymal stem cell acquired immunological tolerance and transdifferentiated to cardiomyocyte in vivo. (2009)
  • Author(s): Hiroko Tsuji, Yukinori Ikegami, Shunichiro Miyoshi, Naoko Hida, Nobuhiro Nishiyama, Ikuko Togashi, Hikaru Nakamizo, Hironori Asada, Taro Uyama, Mamoru Tanaka, Kaoru Segawa, Junko Inoue, Kazuhiro Minegishi, Hitoshi Ishimoto, Satoshi Ogawa, Yasunori Yoshimura, Akihiro Umezawa
  • Organizer: American Heart Association.
  • Place of Presentation: NEWORLEANS
• [Presentation] Human amniotic membrane-derived mesenchymal stem cell acquired immune tolerance by HLA-G expression and differentiated into cardiomyocyte in vivo. (2008)
  • Author(s): Hiroko Tsuji, Yukinori Ikegami, Shunichiro Miyoshi, Naoko Hida, Nobuhiro Nishiyama, Ikuko Togashi, Hikaru Nakamizo, Hironori Asada, Taro Uyama, Mamoru Tanaka, Kaoru Segawa, Junko Inoue, Satoshi Ogawa, Yasunori Yoshimura, Akihiro Umezawa
  • Organizer: Americal College of Cardiology
  • Place of Presentation: CHICAGO
• [Presentation] Xenografted human amniotic membrane-derived mesenchymal stem cells acquired immunologic tolerance and transdifferentiated into cardiomyocytes in vivo. (2008)
  • Author(s): Hiroko Tsuji, Yukinori Ikegami, Shunichiro Miyoshi, Naoko Hida, Nobuhiro Nishiyama, Ikuko Togashi, Hikaru Nakamizo, Hironori Asada, Taro Uyama, Mamoru Tanaka, Kaoru Segawa, Junko Inoue, Satoshi Ogawa, Yasunori Yoshimura, Akihiro Umezawa.
  • Organizer: European Society for Human Reproduction and Embryology
  • Place of Presentation: BALCERONA
• [Remarks] ホームページ等