Comprehensive analysis for extracellular vesicles from endothelial progenitor cells

• Project/Area Number: 18K16956
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Osaka University
• Principal Investigator: Sakimoto Susumu 大阪大学, 医学系研究科, 助教 (60633047)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 血管新生 / 血管内皮コロニー形成細胞 / エクソソーム / 網膜血管 / 血管内皮細胞 / 糖尿病網膜症 / 虚血性網膜症 / パラクライン / 血管再生 / 細胞治療 / neurovascular unit

Outline of Final Research Achievements

Current standard-of-care treatments for diabetic retinopathy, like VEGF antagonists, aim to inhibit neovascularization and vascular leak but do nothing to alleviate the underlying ischemia driving the disease and fail to provide protection to neural cells under hypoxic stress. As natural carriers of miRs and proteins, EVs secreted from endothelial colony forming cells possess a multi-modal mechanism that may promote physiological angiogenesis and preserve damaged neurons, as suggested by our preliminary data demonstrating these agents may present a promising approach to treat these complex disorders.

Academic Significance and Societal Importance of the Research Achievements

本研究成果によって虚血性網膜症に対する新しい治療の可能性が示された。つまり細胞治療では、免疫原性反応を起こす可能性があるのにたいし、治療に用いる細胞由来の小胞を純化・投与することにより、より安全な治療効果をもたらす可能性がある。血管内皮コロニー形成細胞のパラクラインメカニズムの一つの作用として、細胞外小胞は有望であると考えられる。

Research Products

• [Journal Article] Retinal neovascularization-simulating retinal capillary reperfusion in branch retinal vein occlusion, imaged by wide-field optical coherence tomography angiography. (2020)
  • Author(s): Sakimoto S, Kawasaki R, Nishida K.
  • Journal Title: JAMA Ophthalmology Volume: 138 Issue: 2 Pages: 216-218
  • DOI: 10.1001/jamaophthalmol.2019.5018
  • Peer Reviewed
• [Journal Article] Retinal microglia are critical for subretinal neovascular formation. (2020)
  • Author(s): Usui-Ouchi A, Usui Y, Kurihara T, Aguilar E, Dorrell MI, Ideguchi Y, Sakimoto S, Bravo S, Friedlander M.
  • Journal Title: JCI insight Volume: 5 Issue: 12 Pages: 1391-1391
  • DOI: 10.1172/jci.insight.137317
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of Retinal Nonperfusion in Branch Retinal Vein Occlusion Using Wide-Field Optical Coherence Tomography Angiography (2019)
  • Author(s): Shiraki A, Sakimoto S, Tsuboi K, Wakabayashi T, Hara C, Fukushima Y, Sayanagi K, Nishida K, Sakaguchi H, Nishida K.
  • Journal Title: Acta Ophthalmol . Volume: 97 Issue: 6 Pages: 913-918
  • DOI: 10.1111/aos.14087
  • Peer Reviewed
• [Journal Article] Activated Protein C for Ischemic Central Retinal Vein Occlusion: One-Year Results (2019)
  • Author(s): Hara Chikako、Kamei Motohiro、Sakaguchi Hirokazu、Matsumura Nagakazu、Sakimoto Susumu、Suzuki Mihoko、Nishida Kentaro、Fukushima Yoko、Nishida Kohji
  • Journal Title: Ophthalmology Retina Volume: 3 Issue: 1 Pages: 93-94
  • DOI: 10.1016/j.oret.2018.07.012
  • Peer Reviewed
• [Journal Article] Observation of Treated Iris Neovascularization by Swept-Source-Based En-Face Anterior-Segment Optical Coherence Tomography Angiography (2019)
  • Author(s): Shiozaki D, Sakimoto S, Shiraki A, Wakabayashi T, Fukushima Y, Oie Y, Usui S, Sato S, Sakaguchi H, Nishida K.
  • Journal Title: Sci Rep . Volume: 9 Issue: 1 Pages: 10262-10262
  • DOI: 10.1038/s41598-019-46514-z
  • Peer Reviewed / Open Access
• [Journal Article] TAK1 Prevents Endothelial Apoptosis and Maintains Vascular Integrity. (2018)
  • Author(s): Naito H, Iba T, Wakabayashi T, Tai-Nagara I, Suehiro JI, Jia W, Eino D, Sakimoto S, Muramatsu F, Kidoya H, Sakurai H, Satoh T, Akira S, Kubota Y, Takakura N.
  • Journal Title: Dev Cell. Volume: 48 Issue: 2 Pages: 151-166
  • DOI: 10.1016/j.devcel.2018.12.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cross-Sectional Imaging Analysis of Epiretinal Membrane Involvement in Unilateral Open-Angle Glaucoma Severity. (2018)
  • Author(s): Sakimoto S, Okazaki T, Usui S, Ishibashi T, Oura Y, Nishida K, Miki A, Kawasaki R, Matsushita K, Sakaguchi H, Nishida K.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 59 Issue: 15 Pages: 5745-5751
  • DOI: 10.1167/iovs.18-25292
  • Peer Reviewed / Open Access / Int'l Joint Research