Development of 3D culture using cardiac stem cells derived from adult heart and its clinical application

2010 Fiscal Year Final Research Report

• Project/Area Number: 19209047
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: KAWAGUCHI NANAKO Tokyo Women's Medical University, 神経研究所 遺伝子疾患治療研究部, 科研費研究員 (10200700)
• Co-Investigator(Kenkyū-buntansha): SAITOH Satoshi 東京女子医科大学, 医学部, 講師 (60246551) ; MATSUMURA Goki 東京女子医科大学, 医学部, 助教 (20297469)
• Project Period (FY): 2007 – 2010
• Keywords: 心臓幹細胞c-kit / GATA4 / 3次元培養

Research Abstract

The aim of this study is to establish 3D culture for transplantation to the infarcted heart. Cardiac stem cells obtained as c-kit positive cells from adult rat hearts were used as a cell source. Even if we use the same method to obtain c-kit positive cells, different genes expression pattern was observed after the long-term culture. Among the various cardiac stem cells (CSCs), GATA4 high-expressing CSCs showed more potential to differentiate into cardiac myocytes than GATA4 low-expressing cells in vitro. Furthermore, these GATA4 high CSCs had more survival effect on the co-cultured cardiacmyocytes derived from adult rat heart than GATA4 low-expressing CSCs. Therefore,GATA4 high CSCs are the appropriate cell source for regenerative medicine for heart failure. We also showed that TGF-βsuperfamily associates with myogenesis.

Research Products

• [Journal Article] TGF-β Superfamily regulates a switch that mediates differentiation either into adipocytes or myocytes in left atrium derived pluripotent cells (LA-PCs). (2010)
  • Author(s): Kawaguchi N, Yamaguchi M, Nakao R, Ogawa D, Matsuoka R
  • Journal Title: Biochemical and Biophysical Research Communications 396 Pages: 615-625
  • Peer Reviewed
• [Journal Article] Myogenic differentiation in atrium-derived adult cardiac pluripotent cells and the transcriptional regulation of GATA4 and myogenin on ANP promoter (2010)
  • Author(s): Hasan MK, Komoike Y, Tsunesumi S, Nagao H, Nakao R, Matsuoka R, Kawaguchi N
  • Journal Title: Genes to Cells (15) Pages: 439-453
  • Peer Reviewed
• [Journal Article] Micro and nano-scale in vitro 3D culture system for cardiac stem cells. (2010)
  • Author(s): Hosseinkhani H, Hosseinkhani M, Hattori S, Matsuoka R, Kawaguchi N
  • Journal Title: Journal of biomedical materials research, Part A 94A Pages: 1-8
  • Peer Reviewed
• [Journal Article] Characterization of long-term Cultured Cardiac Stem Cells (CSCs) Derived from Adult Rat Hearts (2010)
  • Author(s): Miyamoto S, Kawaguchi N, Ellison G, Matsuoka R, Shin'oka T, Kurosawa H
  • Journal Title: Stem Cells and Devlopment 19, 1 Pages: 105-116
  • Peer Reviewed
• [Journal Article] 遺伝子を導入した骨髄幹細胞の心筋内移植による心筋症治療法の開発 (2010)
  • Author(s): 宮本真嘉,松村剛毅,市原有起,川口奈奈子,八木寿人,松岡瑠美子,黒澤博身
  • Journal Title: (財)日本心臓血圧研究振興会(平成十九年度研究業績集) Pages: 13-6
• [Journal Article] Characterization of c-kit-positive enriched cells isolated from the adult rat heart. (2007)
  • Author(s): Kawaguchi N, Miyamoto S, Ellison GM, Matsuoka R, Shin'oka T
  • Journal Title: Future aspects of Medical Science and Education : Proceedings of the 2nd IREIIMS Open Symposium "Challenge of Integrated Medical Sciences"(Nadal-Ginard B, Takakura K (Eds.) IREIIMS, Tokyo) Pages: 75-76
• [Journal Article] 遺伝子を導入した骨髄幹細胞の心筋内移植による心筋症治療法の開発 (2007)
  • Author(s): 新岡俊治、松村剛毅、宮本真嘉、市原有起、保々恭子、松岡瑠美子、八木寿人、川口奈奈子、黒澤博身
  • Journal Title: (財)日本心臓血圧研究振興会(平成十八年度研究業績集) Pages: 1-4
• [Journal Article] Proteomic comparison of floating spherical aggregates and dish-attached cells of cardiac stem cells.
  • Author(s): Machida M, Takagaki Y, Matsuoka R, Kawaguchi N
  • Journal Title: International Journal of Cardiology (in press)
  • Peer Reviewed
• [Journal Article] Gata4^<high> CSCs foster cardiac myocyte survival.
  • Author(s): Kawaguchi N, Smith A, Waring C, Hasan K, Miyamoto S, Matsuoka R, Ellison GM
  • Journal Title: PLoS ONE 5(12)(in press) Pages: e14297
  • Peer Reviewed
• [Journal Article] Differentiation and Survival Regulators on Adult Cardiac Derived Stem Cells.
  • Author(s): 松村剛毅
  • Journal Title: Vitamins and Hormones, Stem cell regulator Vol.86(invited)
• [Journal Article] Stem cells for cardiac regeneration and possible roles of the Transforming growth factor (TGF)-β family
  • Author(s): 松村剛毅
  • Journal Title: Biomolecular Concepts invited
  • Peer Reviewed
• [Presentation] c-kit^<pos> GATA-4 high Rat Cardiac Stem Cells Foster Adult Cardiomyocyte Survival Through IGF-1 Paracrine Signalling. (2011)
  • Author(s): Kawaguchi N, Smith AJ, Waring CD, Ellison GM
  • Organizer: Keystone Symposia, Stem Cells in Development, Tissue Homeostasis and Disease
  • Place of Presentation: Santa Fe, New Mexico, USA
  • Year and Date: 2011-02-01
• [Presentation] Differentiation of adult rat left atrium-derived pluripotent cells into adipocytes or myocytes is controlled by a switch regulated by the TGF-beta superfamily. (2010)
  • Author(s): 松村剛毅
  • Organizer: American Society for Cell Biology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2010-12-13
• [Presentation] TGF-beta superfamily regulates a switch that mediates differentiation of bulk-cultured adult rat left atrium-derived pluripotent cells (LA-BC) into either adipocytes or myocytes (2010)
  • Author(s): 松村剛毅
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] 成体心臓由来幹細胞を用いた統合再生研究 (2010)
  • Author(s): 川口奈奈子
  • Organizer: Final IREIIMS Open Symposium
  • Place of Presentation: 東京女子医科大学
  • Year and Date: 2010-02-08
• [Presentation] 成体心臓由来幹細胞を対象とした統合再生研究 (2009)
  • Author(s): 川口奈奈子
  • Place of Presentation: 東京(学士会館)
  • Year and Date: 2009-12-13
• [Presentation] Comparing the transcriptional profiles of undifferentiated left atrial pluripotent cells. (2009)
  • Author(s): Nakao R, Kamrul Hasan, Matsuoka R, Kawaguchi N
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] Effect of Micro and Nano-Scale 3D Culture System on Cardiac Stem Cells (2009)
  • Author(s): Hosseinkhani H, Hosseinkhani M, Nakao R, Miyamoto S, Hattori S, Matsuoka R, Kawaguchi N
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] Identification of the genes involved in signal transduction during myogenesis by using LA-PCs. (2009)
  • Author(s): Kawaguchi N, Nakao R, Matsuoka R
  • Organizer: American Society for Cell Biology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2009-12-06
• [Presentation] International Society for Stem Cell Research (2009)
  • Author(s): Hosseinkhani H, Hosseinkhani M, Hattori S, Matsuoka R, Kawaguchi N Development of 3D culture system for implanting cardiac stem cells from adult rat hearts by combinational technology of 3D tissue engineered scaffold perfusion bioreactor.
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2009-07-09
• [Presentation] Characterization of cultured c-kit positive cardiac stem cells derived from adult. (2008)
  • Author(s): Kawaguchi N, Miyamoto S, Ellison GM, Hasan MK, Matsuoka R
  • Organizer: American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-12-17
• [Presentation] Synergistic Activation of Atrial Natriuretic Peptide (ANP) Promoter by GATA4 and Myogenin (2008)
  • Author(s): M.Kamrul Hasan, Shinka Miyamoto, Rumiko Matsuoka, Nanako Kawaguchi
  • Organizer: American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-12-17
• [Presentation] ラット心臓由来幹細胞の心筋細胞への延命効果に関する研究 (2008)
  • Author(s): 川口奈奈子、宮本真嘉、Kamrul Hasan,Georgina Ellison,松岡瑠美子
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] Characterization of Left Atrium Derived Cardiac Stem Cells. (2008)
  • Author(s): M.Kamrul Hasan, Shinka Myamoto, Rumiko Matsuoka, Nanako Kawaguchi
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 成体ラット心臓由来幹細胞の再生医療への応用 (2008)
  • Author(s): 川口奈奈子,宮本真嘉
  • Organizer: 日本女性科学者の会
  • Place of Presentation: 東京(学士会館)
  • Year and Date: 2008-11-16
• [Presentation] Proteomic analysis of cardiac stem cells derived from adult rat hearts : comparison of the sphere and adherent states of a cardiosphere forming cell clone by protein profiling. (2008)
  • Author(s): Nanako Kawaguchi, Mitsuyo Machida, Rumiko Matsuoka, Yohtaroh Takagaki
  • Organizer: American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-09
• [Presentation] 幹細胞の治療への応用における細胞生物学者からみた現状と問題および将来への期待 (2008)
  • Author(s): 川口奈奈子
  • Organizer: ニッピマトリクス研究所講演
  • Place of Presentation: ニッピマトリクス研究所
  • Year and Date: 2008-09-25
• [Presentation] Characterization of cardiac stem cells derived from adult rat heart. (2007)
  • Author(s): 松村剛毅
  • Organizer: 3^<rd> IREIIMS Symposium.
  • Place of Presentation: 東京女子医科大学
  • Year and Date: 20070000
• [Presentation] 成体ラット心臓由来幹細胞の性質決定と心筋細胞への分化 (2007)
  • Author(s): 川口奈奈子、宮本真嘉、Ellison G.,松村剛毅、松岡瑠美子
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 20070000
• [Presentation] Characterization of cultured c-kit positive cells derived from adult rat heart (2006)
  • Author(s): Kawaguchi N, Miyamoto S, Matsuoka R, Shinoka T
  • Organizer: 2nd IREIIMS Symposium.
  • Place of Presentation: 東京女子医科大学
  • Year and Date: 20060000
• [Presentation] Proteome Analysis of Cardiosphere from Adult RatHearts : Comparison of Spherical and Adherent State of Cardiac Stem Cells成体ラット心臓由来幹細胞のプロテオーム解析:培養条件により誘導された球状塊cardiosphere及び非球状接着状態の比較
  • Author(s): Mitsuyo Machida, Yohtaroh Takagaki, Shinka Miyamoto, Rumiko Matsuoka, Nanako Kawaguchi
  • Organizer: 2008日本分子生物学会、春季シンポジウム
  • Place of Presentation: 札幌