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Umbilical cord extracts improve diabetic abnormalities in bone marrow-derived mesenchymal stem cells and increase their therapeutic effects on diabetic nephropathy

Research Project

Project/Area Number 26460279
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General anatomy (including histology/embryology)
Research InstitutionSapporo Medical University

Principal Investigator

NAGAISHI KANNA  札幌医科大学, 医学部, 講師 (30544118)

Co-Investigator(Kenkyū-buntansha) 藤宮 峯子  札幌医科大学, 医学部, 教授 (10199359)
有村 佳昭  札幌医科大学, 医学部, 研究員 (80305218)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords間葉系幹細胞 / 糖尿病性腎症 / 骨髄間葉系幹細胞
Outline of Final Research Achievements

Bone marrow-derived mesenchymal stem cells (BM-MSC) has been applied as the most valuable source of autologous cell transplantation for diabetic complications. However, hyperglycemia may cause abnormalities in intrinsic BM-MSC which might lose sufficient therapeutic effects in diabetic patients. We demonstrated the functional abnormalities in BM-MSC derived from diabetes models (DM-MSC) in vitro, which resulted in loss of therapeutic effects in vivo in diabetic nephropathy (DN). Then, we developed a novel method to improve abnormalities in BM-MSC using human umbilical cord extracts, namely Wharton’s jelly extract supernatant (WJs). WJs ameliorated proliferative capacity, motility, mitochondrial degeneration, endoplasmic reticular functions in DM-MSC. DM-MSC activated by WJs ameliorated renal injury in DN. In this study, we developed a novel activating method using WJs to significantly increase the therapeutic effect of BM-MSC, which may allow effective autologous cell transplantation.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015 2014 2013

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Umbilical cord extracts improve diabetic abnormalities in bone marrow-derived mesenchymal stem cells and increase their therapeutic effects on diabetic nephropathy.2017

    • Author(s)
      Nagaishi K, Mizue Y, Chikenji T, Otani M, Nakano M, Saijo Y, Tsuchida H, Ishioka S, Nishikawa A, Saito T, Fujimiya M.
    • Journal Title

      Scientific Reports

      Volume: 7:8484 Issue: 1 Pages: 1-17

    • DOI

      10.1038/s41598-017-08921-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes.2016

    • Author(s)
      Nagaishi K, Mizue Y, Chikenji T, Otani M, Nakano M, Konari N, Fujimiya M.
    • Journal Title

      Sci Rep.

      Volume: 6:34842 Issue: 1 Pages: 1-16

    • DOI

      10.1038/srep34842

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mesenchymal stem cell therapy ameliorates diabetic hepatocyte damage in mice by inhibiting infiltration of bone marrow-derived cells.2013

    • Author(s)
      Nagaishi K, Ataka K, Echizen E, Arimura Y, Fujimiya M
    • Journal Title

      Hepatology

      Volume: Epub ahead of print Issue: 5 Pages: 1816-29

    • DOI

      10.1002/hep.26975

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Mitochondria transfer of bone marrow-derived mesenchymal stem cells inhibits apoptosis in proximal tubular epithelial cells in diabetic nephropathy.2017

    • Author(s)
      Konari N, Nagaishi K, Kikuchi S, Mizue Y, Nakano M, Chikenji T, Otani M, Saito Y, Fujimiya M.
    • Organizer
      International Society for stem cell research (ISSCR) 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 自己骨髄間葉系幹細胞を用いた糖尿病性腎症の治療2016

    • Author(s)
      永石歓和
    • Organizer
      第28回北海道輸血シンポジウム
    • Place of Presentation
      北海道(札幌)、日本赤十字社北海道ブロック血液センター3階研修室
    • Year and Date
      2016-07-09
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 胎児付属物抽出液で賦活化した骨髄間葉系幹細胞による糖尿病性腎症の新規治療法の開発2016

    • Author(s)
      永石歓和、水江由佳、千見寺貴子、大谷美穂、中野正子、 小成直人、藤宮峯子
    • Organizer
      第28回代用臓器・再生医学研究会総会
    • Place of Presentation
      北海道大学 鈴木章記念ホール(北海道、札幌)
    • Year and Date
      2016-02-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 糖尿病性腎症に対する自己骨髄間葉系幹細胞治療の課題と最適化法の開発2015

    • Author(s)
      永石歓和、水江由佳、小成直人、千見寺貴子、中野正子、藤宮峯子
    • Organizer
      第36回日本炎症再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都・港区)
    • Year and Date
      2015-07-21 – 2015-07-22
    • Related Report
      2014 Research-status Report
  • [Presentation] 糖尿病性腎症に対する自己骨髄間葉系幹細胞治療の課題と最適化法の開発2015

    • Author(s)
      永石歓和、水江由佳、小成直人、千見寺貴子、中野正子、藤宮峯子
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都、港区)
    • Year and Date
      2015-07-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 自己骨髄間葉系幹細胞を用いた糖尿病性腎症治療の課題と最適化2015

    • Author(s)
      永石歓和、小成直人、水江由佳、中野正子、千見寺貴子、藤宮峯子
    • Organizer
      第14回日本再生医療学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Research-status Report
  • [Presentation] 自己骨髄間葉系幹細胞を用いた糖尿病合併症の新規治療戦略2014

    • Author(s)
      永石歓和、藤宮峯子
    • Organizer
      第35回日本炎症・再生医学会
    • Place of Presentation
      万国津梁館(沖縄県・名護市)
    • Year and Date
      2014-07-01 – 2014-07-04
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Novel therapeutic strategy for diabetic nephropathy using optimally pre-conditioned self-bone marrow derived mesenchymal stem cells in mice.2014

    • Author(s)
      Kanna Nagaishi, Naoto Konari, Koji Ataka, Masako Nakano, Kozoh Ishikawa, Mineko Fujimiya
    • Organizer
      International Society for stem cell research (ISSCR) 2014、第12回国際幹細胞学会
    • Place of Presentation
      バンクーバー、カナダ
    • Year and Date
      2014-06-19 – 2014-06-22
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 間葉系幹細胞の賦活化剤、賦活化された間葉系幹細胞およびその製造方法2015

    • Inventor(s)
      藤宮峯子、永石歓和、水江由佳、千見寺貴子
    • Industrial Property Rights Holder
      藤宮峯子、永石歓和、水江由佳、千見寺貴子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-03-11
    • Related Report
      2014 Research-status Report
    • Overseas

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Published: 2014-04-04   Modified: 2019-03-29  

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