Development of multi-growth factor secreted fetal membrane-derived mesenchymal stem cell sheets

2013 Fiscal Year Final Research Report

• Project/Area Number: 23700569
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biological material science
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: ISHIKANE Shin 独立行政法人国立循環器病研究センター, 研究所, 客員研究員 (40470190)
• Project Period (FY): 2011 – 2013
• Keywords: 卵膜 / 間葉系幹細胞 / 細胞シート / パラクライン / 心筋梗塞 / 血管新生効果

Research Abstract

To develop effective treatments for chronic heart failure, we used fetal membrane (FM) derived mesenchymal stem cell (MSC) sheets. In a rat chronic myocardial infarction (MI) model, the allogeneic FM-MSC sheets transplantation had significantly reversed wall thinning in the scar area and had improved cardiac function as well as the autologous bone marrow derived MSC sheets transplantation. However, the allogeneic FM-MSC sheets transplantation did not improve cardiac function in a mini-pig MI model. To improve secretion of angiogenic factors from the FM-MSC sheets, we transfected siRNA-int6 to the FM-MSC. The siRNA-int6 transfection reduced the int6 expression in the FM-MSC, however did not increase the HIF2alpha, HIF1 and VEGF expressions. In a mini-pig acute MI model, angiogenic effect was observed by intra myocardial injection of the siRNA-int6 plasmid-GenomeONE mixture.

Research Products

• [Journal Article] Allogeneic transplantation of fetal membrane-derived mesenchymal stem cell sheets increases neovascularization and improves cardiac function after myocardial infarction in rats (2013)
  • Author(s): Shin Ishikane, Hiroshi Hosoda, Kenichi Yamahara, Yoshiharu Akitake, Jung Kyoungsook, Kenichi Mishima, Katsunori Iwasaki, Michihiro Fujiwara, Mikiya Miyazato, Kenji Kangawa, Tomoaki Ikeda
  • Journal Title: Transplantation Volume: 96 Pages: 697-706
  • DOI: 10.1097/TP.0b013e31829f753d
  • Peer Reviewed
• [Journal Article] 卵膜由来の間葉系幹細胞を用いた再生医療の将来 (2011)
  • Author(s): 石兼真,池田智明
  • Journal Title: Biophilia Volume: 第7巻第3号 Pages: 38-43
  • URL: http://biophilia.jp/journal/biophilia-27.html
• [Journal Article] 卵膜由来間葉系幹細胞の再生医療応用を目的とした治療効果ならびに安全性に関する研究 (2011)
  • Author(s): 石兼真
  • Journal Title: 福岡大学薬学集報 Volume: 第11巻35号 Pages: 17-25
  • URL: http://www.adm.fukuoka-u.ac.jp/fu844/home2/Ronso/Yakugaku/P11-1/P11-1mokuji.htm
• [Presentation] Int6抑制による血管新生の機序解明と臨床応用 (2012)
  • Author(s): 早川英毅,小野富男,石兼真,秋武義治,細田洋司,風間智彦,松本太郎,池田智明,芝崎太
  • Organizer: Conference for Biosignal Medicine 2012
  • Place of Presentation: 三重
  • Year and Date: 20120831-0902
• [Presentation] 慢性心筋梗塞に対する卵膜由来間葉系幹細胞シートの他家移植による心機能改善効果、生着性に関する検討 (2011)
  • Author(s): 石兼真,Jung Kyongsook,上田恵子,桂木真司,根木玲子,山中薫,池田智明
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 20110829-31
• [Presentation] 卵膜由来間葉系幹細胞を用いた再生医療における他家細胞移植療法の確立 (2011)
  • Author(s): 石兼真,細田洋司, Jung Kyongsook,秋武善治,三島健一,岩崎克典,藤原道弘,早川英毅,芝崎太,池田智明
  • Organizer: Conference for Biosignal Medicine 2011
  • Place of Presentation: 長野
  • Year and Date: 20110624-26
• [Book] Therapeutic application of allogeneic feral membrane-derived mesenchymal stem cell transplantation in regenerative medicine (2012)
  • Author(s): Shin Ishikane, Hiroshi Hosoda, Tomoaki Ikeda
  • Total Pages: 221-236
  • Publisher: Intech. Tissue Regeneration.