Regerative medicine for vocal fold scar with cell therapy

• Project/Area Number: 25462680
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kyoto University
• Principal Investigator: Hirano Shigeru 京都大学, 医学(系)研究科(研究院), 准教授 (10303827)
• Co-Investigator(Kenkyū-buntansha): KANEMARU Shin-ichi 田附興風会北野病院, 部長 (00271510) ; NAKAMURA Tatsuo 京都大学, 再生医科学研究所, 准教授 (70227908) ; TATEYA Ichiro 京都大学, 大学院医学研究科, 講師 (20526363) ; KITAMURA Morimasa 京都大学, 大学院医学研究科, 助教 (60543262)
• 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: 声帯 / 再生医療 / 幹細胞 / 声帯瘢痕 / 細胞治療 / コラーゲン / ジェラチン / 線維芽細胞増殖因子 / 増殖因子 / 再生土台 / 再生 / 喉頭 / 単核球

Outline of Final Research Achievements

This research aims to develop regenerative medicine for the vocal fold with cell transplant. Mesenchymal stem cells derived from the bone marrow or fat improved histological and functional aspects of canine scarred vocal folds. ASC showed higher gene expression of HAS and HGF from vocal fold cells, which appeared beneficial for vocal fold regeneration. Collagen/gelatin scaffold was developed that control-release growth factors. The scaffold proved a good biocompatibility to vocal fold fibroblasts, and indicated regenerative effects on canine vocal fold scar.

Research Products

• [Journal Article] The efficacy of a novel collagen-gelatin scaffold with basic fibroblast growth factor for the treatment of vocal fold scar. (2016)
  • Author(s): Hiwatashi, N., Hirano, S., Mizuta, M., Kobayashi, T., Kawai, Y., Kanemaru, SI., Nakamura, T., Ito, J., Kawai, K., Suzuki, S.
  • Journal Title: J Tissue Eng Regen Med. Volume: in press Issue: 5 Pages: 0-0
  • DOI: 10.1002/term.2060
  • Peer Reviewed
• [Journal Article] Biocompatibility and Efficacy of Collagen/Gelatin Sponge Scaffold With Sustained Release of Basic Fibroblast Growth Factor on Vocal Fold Fibroblasts in 3-Dimensional Culture. (2015)
  • Author(s): Hiwatashi, N., Hirano, S., Mizuta, M., Tateya, I., Kanemaru, SI., Nakamura, T., Ito, J., Kawai, K., Suzuki, S.
  • Journal Title: Ann Otol Rhinol Laryngol. Volume: 124 Issue: 2 Pages: 116-25
  • DOI: 10.1177/0003489414546396
  • Peer Reviewed
• [Journal Article] Comparison of ASCs and BMSCs combined with atelocollagen for vocal fold scar regeneration. (2015)
  • Author(s): Hiwatashi N, Hirano S, Suzuki R, Kawai Y, Mizuta M, Kishimoto Y, tateya I, Kanemaru S, Nakamura T, Dezawa M, Ito J.
  • Journal Title: Laryngoscope Volume: 0 Issue: 5 Pages: 0-0
  • DOI: 10.1002/lary.25667
  • Peer Reviewed
• [Journal Article] The effect of astaxanthin on vocal fold wound healing. (2014)
  • Author(s): Mizuta M, Hirano S, Hiwatashi N, Tateya I, Kanemaru SI, Nakamura T, Ito J.
  • Journal Title: Laryngoscope Volume: 124
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Restoration of Scarred Vocal Folds Using 5 Amino Acid-Deleted Type Hepatocyte Growth Factor (2014)
  • Author(s): Mizuta M, Hirano S, Ohno S, Kanemaru S, Nakamura T, Ito J.
  • Journal Title: Laryngoscope Volume: 124
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Vocal Fold Fibroblast Response to Growth Factor Treatment is Age Dependent: Results From an In Vitro Study. (2014)
  • Author(s): Graupp M, Kiesler K, Friedrich G, Ainödhofer H, Gruber HJ, Kieslinger P, Saxena A, Hirano S, Gugatschka M.
  • Journal Title: J Voice Volume: 28 Pages: 420-423
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and safety of human recombinant hepatocyte growth factor administered to vocal folds. (2014)
  • Author(s): Mizuta M, Hirano S, Kishimoto Y, Hiwatashi N, Tateya I, Kanemaru S, Nakamura T, Ito J.
  • Journal Title: Laryngoscope. Volume: 124 Pages: 2131-2135
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Age effects on extracellular matrix production of vocal fold scar fibroblasts in rats. (2014)
  • Author(s): Gugatschka M, Ainodhofer H, Gruber H, Graupp M, Kieslinger P, Kiester K, Saxena A, Hirano S, Friedrich G.
  • Journal Title: Eur Arch Otorhinolaryngol Volume: 271 Pages: 1107-1112
  • Peer Reviewed
• [Journal Article] Regenerative phonosurgical treatments for vocal fold scar and sulcus with basic fibroblast growth factor. (2013)
  • Author(s): Hirano S, Mizuta M, Kaneko M, Tateya I, Kanemaru SI, Ito J.
  • Journal Title: Laryngoscope. Volume: 123 Pages: 2749-2755
  • Peer Reviewed
• [Journal Article] Functional regeneration of laryngeal muscle using bone marrow-derived stromal cells (2013)
  • Author(s): Kanemaru SI, Kitani Y, Ohno S, Shigemoto T, Kojima T, Ishikawa S, Mizuta M, Hirano S, Nakamura T, Dezawa M.
  • Journal Title: Laryngoscope Volume: Epub
  • NAID: 10031144966
  • Peer Reviewed
• [Presentation] Current status of intracordal injectino of basic fibroblast growth factor for vocal fold scar and atrophy. (2015)
  • Author(s): Hirano S, Kishimoto Y, Hiwatashi N, Kaneko M.
  • Organizer: 44th Voice Foundation Symposium
  • Place of Presentation: Philadelpha
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] Comparison of the efficacy of mesenchymal stromal cells for canine vocal fold regeneration: Adipose-derived stromal cells versis bone marrow-derived stromal cells. (2015)
  • Author(s): Hiwatashi N, Kawai Y, Kishimoto Y, Tsuji T, Suzuki R, Hirano S
  • Organizer: 136th annula meeting of American Laryngological Association
  • Place of Presentation: Boston
  • Year and Date: 2015-05-22
  • Int'l Joint Research
• [Presentation] Prevention of vocal fold scarring with local application of basic fibroblast growth factor in rat model. (2015)
  • Author(s): Suzuki R, Hirano S, Tateya I, Kishimoto Y, Kawai Y, Hiwatashi N.
  • Organizer: 95th annual meeting of American Bronchoesophagological Association
  • Place of Presentation: Boston
  • Year and Date: 2015-05-22
  • Int'l Joint Research
• [Presentation] Tissue engineering approach to regeneration of the larynx with growth factors. (2014)
  • Author(s): Hirano S
  • Organizer: 13th Biennial Phonosurgery Symposium -Strategic Directions in Laryngeal Tissue Regeneration
  • Place of Presentation: Madison
  • Year and Date: 2014-07-10 – 2014-07-12
  • Invited
• [Presentation] Growth factor for treatment of vocal fold scar. (2014)
  • Author(s): Hirano S.
  • Organizer: Garnd Round Univeristy of Pittsburgh Medical Center,
  • Place of Presentation: Pittsburgh
  • Year and Date: 2014-05-23
  • Invited
• [Presentation] Acute vocal fold scar restoration with injectable basic fibroblast growth factor hydrogel. (2014)
  • Author(s): Kobayashi T, Hirano S, Mizuta M, Hiwatashi N, Kishimoto Y, Ito J.
  • Organizer: 94th American Bronchoesophagological Association
  • Place of Presentation: Las Vegas
  • Year and Date: 2014-05-14 – 2014-05-15
• [Presentation] Identification of slow cycling cells in the macula flava of rat vocal fold. (2014)
  • Author(s): Kawai Y, Hirano S, Kishimoto Y, Ito J.
  • Organizer: 94th American Bronchoesophagological Association
  • Place of Presentation: Las Vegas
  • Year and Date: 2014-05-14 – 2014-05-15
• [Presentation] Growth , age, and regeneration of the vocal fold. (2014)
  • Author(s): Hirano S.
  • Organizer: 6th International Course on Laryngostroboscopy and Fiberendoscopic Phonosurgery
  • Place of Presentation: Cesena
  • Year and Date: 2014-04-01 – 2014-04-02
  • Invited
• [Presentation] Regenerative treatments for vocal fold scar and sulcus with basic fibroboast growth factor (2013)
  • Author(s): Hirano S, Kaneko M, Tateya I, Kanemaru S, Ito J.
  • Organizer: 134th American Laryngological Association
  • Place of Presentation: Orlando
• [Presentation] Effect of Asthaxanthin on vocal fold wound healing (2013)
  • Author(s): Mizuta M, Tateya I, Hiwatashi N, Kanemaru S, Ito J, Hiraon S.
  • Organizer: 134th American Laryngological Association
  • Place of Presentation: Orlando
• [Presentation] Regeneration potential of chronically scarred vocal fold fibroblasts: An in vitro study (2013)
  • Author(s): Gugatschka M, Ainoedhofer H, Friedrich G, Gruber H, Kiesler K, Saxena A, Hirano S.
  • Organizer: 93rd American Bronchesophagological Association
  • Place of Presentation: Orlando
• [Presentation] Innovation of regenerative medicine for the larynx. (2013)
  • Author(s): Hirano S.
  • Organizer: 2nd European Academy of ORL-HNS
  • Place of Presentation: Nice
  • Invited
• [Presentation] Surgical treatment of vocal fold scar using basic fibroblast growth factor. International Association of Phonosurgery (2013)
  • Author(s): Hirano S.
  • Organizer: 10th Pan-European Voice Conference
  • Place of Presentation: Praque
  • Invited
• [Book] International perspective on voice disorders. Chapter:Contemporary voice research in Japan. (2013)
  • Author(s): Hirano S.
  • Total Pages: 12
  • Publisher: Multilingual Matters
• [Remarks] 京都大学耳鼻咽喉科
  • URL: http://www.kuhp.kyoto-u.ac.jp/~ent/