Regeneration of ocular surface fibrosis by human mesenchymal stem cell transplantation

• Project/Area Number: 25462759
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Wakayama Medical University
• Principal Investigator: YAMANAKA Osamu 和歌山県立医科大学, 医学部, 博士研究員 (50254545)
• Co-Investigator(Kenkyū-buntansha): SAIKA Shizuya 和歌山県立医大, 医学部, 教授 (40254544)
• Research Collaborator: KAO Winston シンシナティ大学, 医学部, 教授
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 創傷治癒 / 幹細胞 / 線維化 / 国際情報交換 / シグナル / サイトカイン

Outline of Final Research Achievements

We investigated the biological functions of human umbilical mesenchymal stem cells (hUMSC). hUMSC suppressed scar formation of alkali burn mouse model. Our findings showed that hUMSC mediated the activation of growth factors or cytokines such as TGFβ andTNFα to suppress fibrosis. We suggested that TNFα and βcatenin deeply associated the process of scar formation. hUMSC could be a novel alternative for treating ocular surface fibrosis.

Research Products

• [Int'l Joint Research] University of Cincinnati(米国)
• [Journal Article] Inhibition of development of laser-induced choroidal neovascularization with suppression of infiltration of macrophages in Smad3-null mice. (2016)
  • Author(s): Iwanishi H, Fujita N, Tomoyose K, Okada Y, Yamanaka O, Flanders KC, Saika S.
  • Journal Title: Lab Invest. Volume: e-journal Issue: 6 Pages: 641-51
  • DOI: 10.1038/labinvest.2016.30
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pathobiology of wound healing after glaucoma filtration surgery. (2015)
  • Author(s): Yamanaka O, Kitano-Izutani A, Tomoyose K, Reinach PS.
  • Journal Title: BMC Ophthalmol. Volume: 15 Issue: S1 Pages: 157-157
  • DOI: 10.1186/s12886-015-0134-8
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Suppression of In Vivo Neovascularization by the Loss of TRPV1 in Mouse Cornea. (2015)
  • Author(s): Tomoyose K, Okada Y, Sumioka T, Miyajima M, Flanders KC, Shirai K, Morii T, Reinach PS, Yamanaka O, Saika S.
  • Journal Title: J Ophthalmol. Volume: Sep 27 Pages: 706404-706404
  • DOI: 10.1155/2015/706404
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Histological analysis of a cornea following experimental femtosecond laser ablation. (2014)
  • Author(s): Sumioka T, Miyamoto T, Takatsuki R, Okada Y, Yamanaka O, Saika S.
  • Journal Title: Cornea. Volume: 33 Issue: Supplement 11 Pages: 19-24
  • DOI: 10.1097/ico.0000000000000251
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of the loss of conjunctival Muc16 on corneal epithelium and stroma in mice. (2014)
  • Author(s): Shirai K, Okada Y, Cheon DJ, Miyajima M, Behringer RR, Yamanaka O, Saika S.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 55 Issue: 6 Pages: 3626-3637
  • DOI: 10.1167/iovs.13-12955
  • Peer Reviewed / Open Access
• [Journal Article] Impairment of corneal epithelial wound healing in a TRPV1-deficient mouse. (2014)
  • Author(s): Sumioka T, Okada Y, Reinach PS, Shirai K, Miyajima M, Yamanaka O, Saika S.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 55 Issue: 5 Pages: 3295-3302
  • DOI: 10.1167/iovs.13-13077
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 組織修復におけるmatricellular proteinの役割 (2014)
  • Author(s): 山中 修 雑賀司珠也
  • Journal Title: 医学の歩み Volume: 248 Pages: 515-522
• [Journal Article] Lumican Binds ALK5 to Promote Epithelium Wound Healing (2013)
  • Author(s): Osamu Yamanaka, Yong Yuan, Vivien Jane Coulson-Thomas, Tarsis Ferreira Gesteira, Mindy K. Call, Yujin Zhang, Jianhua Zhang, Shao-Hsuan Chang, Changchun Xie, Chia-Yang Liu, Shizuya Saika, James V. Jester, Winston W-Y Kao
  • Journal Title: PLOS one Volume: 8 Issue: 12 Pages: e82730-e82730
  • DOI: 10.1371/journal.pone.0082730
  • Peer Reviewed
• [Journal Article] Increased fragility, impaired differentiation, and acceleration of migration of corneal epithelium of epiplakin-null mice. (2013)
  • Author(s): Kokado M, Okada Y, Goto M, Ishikawa K, Miyamoto T, Yamanaka O, Fujiwara S, Saika S
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 54 Issue: 5 Pages: 3780-9
  • DOI: 10.1167/iovs.12-11077
  • Peer Reviewed
• [Journal Article] modulation of wound healing response in the corneal stroma by osteopontin and tenascin-C. (2013)
  • Author(s): Saika S, Sumioka T, Okada Y, Yamanaka O, Kitano A, Miyamoto T, Shirai K, Kokado H.
  • Journal Title: Ocul Surf. Volume: 11 Issue: 1 Pages: 12-15
  • DOI: 10.1016/j.jtos.2012.09.002
  • Peer Reviewed
• [Journal Article] Impaired cornea wound healing in a tenascin C-deficient mouse model. (2013)
  • Author(s): Sumioka T, Kitano A, Flanders KC, Okada Y, Yamanaka O, Fujita N, Iwanishi H, Kao WW, Saika S.
  • Journal Title: Lab Invest. Volume: 93 Pages: 207-217
  • Peer Reviewed
• [Presentation] EDMT and matricellular protein (2016)
  • Author(s): Osamu Yamanaka
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 2016-04-07
  • Int'l Joint Research / Invited
• [Presentation] 結膜創傷治癒過程でのTGFβ/β-cateninクロスオーバー (2015)
  • Author(s): 山中 修 友寄勝夫 雑賀司珠也
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2015-04-16
• [Presentation] 培養ヒト結膜線維芽細胞でのTGFb/bcateninクロスオーバー (2014)
  • Author(s): 山中 修 友寄勝夫 Winston WY Kao 雑賀司珠也
  • Organizer: 日本緑内障学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-09-19 – 2014-09-21
• [Presentation] Effects of β-catenin inhibitor, ICG-001, on cultured human conjunctival fibroblast (2014)
  • Author(s): Osamu Yamanaka, Winston WY Kao, Shizuya Saika
  • Organizer: The Association for Research in vision and Ophthalmology
  • Place of Presentation: Florida, USA
  • Year and Date: 2014-05-04 – 2014-05-08
• [Presentation] β-catenin阻害の培養結膜線維芽細胞に対する影響 (2014)
  • Author(s): 山中 修 雑賀司珠也
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-02 – 2014-04-06
• [Presentation] Loss of TNFα accelerates inflammatory fibrosis during wound healing in conjunctiva in mice. (2014)
  • Author(s): Osamu Yamanaka
  • Organizer: Gordon research conference
  • Place of Presentation: Bentura USA
• [Presentation] Endogenous TNFα is required for normal tissue repair in mouse conjunctiva (2013)
  • Author(s): Osamu Yamanaka, Ai Kitano, Yuka Okada, Winston W-Y Kao, Shizuya Saika
  • Organizer: ARVO
  • Place of Presentation: Seattle, USA
• [Presentation] 結膜創傷治癒におけるTNFαの役割 (2013)
  • Author(s): 山中 修 泉谷 愛 岡田由香 Winston Kao 雑賀司珠也
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] ルミカンの創傷治癒における機序と可能性 (2013)
  • Author(s): 山中 修
  • Organizer: 日本結合組織学会
  • Place of Presentation: 和歌山
  • Invited