Development of novel strategy for suppressing chronic inflammation in adipose tissues utilizing adipose-derived stem cells.

• Project/Area Number: 15K21251
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics; Drug development chemistry
• Research Institution: Kindai University (2016); University of the Ryukyus (2015)
• Principal Investigator: ISHIDA Masayoshi 近畿大学, 医学部, 助教 (50643251)
• Research Collaborator: TATSUMI Kohei 近畿大学, 医学部, 講師 (70555432) ; KAJI Hiroshi 近畿大学, 医学部, 教授 (90346255)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 間葉系幹細胞 / 慢性炎症 / 2型糖尿病 / 脂肪由来幹細胞 / メタボリックシンドローム / アディポカイン / 脂肪組織由来間葉系幹細胞 / 分化誘導

Outline of Final Research Achievements

Adipose-derived stem cells (ADSCs) were obtained from mouse subcutaneous adipose tissues digested by collagenase and centrifugation. Next, anti-inflammatory effects of ADSCs on the adipose tissues were examined in vitro culture system. In brief, the adipocytes were cultured in the addition of ADSC culture supernatant and the cells were analyzed the expressions of good and bad adipokines. We found out bad adipokines were decreased, on the other hand, good adipokines were not changed by the addition of ADSC supernatant.
Further we examined the beneficial effect of ADSCs on the Type 2 diabetic mice. The mice were divided to two groups to be subjected to ADSC sheet transplantation and sham operation groups, respectively. After the operation,on Day 10, we performed the insulin tolerance test and found out the insulin resistance were recovered by ADSC transplantation compared with the sham operation.

Research Products

• [Journal Article] Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice. (2017)
  • Author(s): Kina-Tanada M, Sakanashi M, Tanimoto A, Kaname T, Matsuzaki T, Noguchi K, Uchida T, Nakasone J, Kozuka C, Ishida M, Kubota H, Taira Y, Totsuka Y, Kina SI, Sunakawa H, Omura J, Satoh K, Shimokawa H, Yanagihara N, Maeda S, Ohya Y, Matsushita M, Masuzaki H, Arasaki A, Tsutsui M.
  • Journal Title: Diabetologia. Volume: 60 Issue: 6 Pages: 1138-1152
  • DOI: 10.1007/s00125-017-4259-6
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Protective Role of Myelocytic Nitric Oxide Synthases in Hypoxic Pulmonary Hypertension in Mice. (2016)
  • Author(s): Masato Tsutsui , Masayoshi Ishida, Katsuhiko Noguchi, Hiroaki Shimokawa
  • Organizer: The 80th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-03-18
• [Presentation] Complete Disruption of All Nitric Oxide Synthases Markedly Reduces Cerebral Infarct Size after Middle Cerebral Artery Occlusion in Mice (2016)
  • Author(s): Masato Tsutsui, Haruaki Kubota, Katsuhiko Noguchi, Masayoshi Ishida, Hiroaki Shimokawa, Yusuke Ohya
  • Organizer: The 80th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-03-18
• [Presentation] 脂肪由来幹細胞（ADSC）の増殖と分化における一酸化窒素合成酵素（NOS）系の役割 (2016)
  • Author(s): 石田昌義、塚原成俊、村上明一、角南寛、岸本英博、筒井正人.
  • Organizer: 日本再生医療学会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-03-17
• [Presentation] Complete Disruption of All Nitric Oxide Synthases Markedly Reduces Cerebral Infarct Size After Middle Cerebral Artery Occlusion in Mice (2015)
  • Author(s): Masato Tsutsui, Kubota Haruaki, Katsuhiko Noguchi, Toshihiro Matsuzaki, Fumiya Hattori, Mayuko Sakanashi, Mika Kina-Tanada, Masayoshi Ishida, Junko Nakasone, Hiroaki Shimokawa, Yusuke Ohya, Kazuhiro Sugahara, Manabu Kakinohana
  • Organizer: American Heart Association Scientific Sessions 2015
  • Place of Presentation: Orange County Convention Center, Orlando, FL, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research