Novel treatment for endometriosis using latent TGF-beta apheresis

• Project/Area Number: 17K11273
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Shunichiro Tsuji 滋賀医科大学, 医学部, 講師 (30601546)
• Co-Investigator(Kenkyū-buntansha): 村上 節 滋賀医科大学, 医学部, 教授 (20240666) ; 山中 章義 滋賀医科大学, 医学部, 医員 (60452249) ; 林 香里 滋賀医科大学, 医学部, 助教 (70569251)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 子宮内膜症 / カニクイザル / TGF-β / カラム治療 / 女性医学 / 不妊症

Outline of Final Research Achievements

We revealed increases in the proportions of resting Tregs and effector Tregs in the peritoneal fluid of women with endometriosis, as well as reduced expression of latency-associated peptide (LAP) on macrophages, resulting in the release of activated TGF-β. These observations may be associated with suppressed immune responses, which may initiate and promote endometriosis in the pelvic cavity.　Next, we demonstrated that endometriosis is a progressive disease in cynomolgus monkeys as reported in humans by performing monthly laparoscopy. These findings also showed most sites of endometriosis were observed in the vesicouterine pouch, and an endometrial cyst of the ovary, which is the most common site of human endometriosis, was not observed. Furthermore, we could establish the scoring system for endometriosis in cynomolgus monkeys.

Academic Significance and Societal Importance of the Research Achievements

本研究では子宮内膜症患者の腹水中マクロファージがTGF-βの産生源であることが示唆され、その制御により治療につながる可能性が考えられた。また、カニクイザルの子宮内膜症がヒトと同様に進行性の病変であることを確認し、腹腔鏡観察による評価方法を作成したことで、子宮内膜症治療の動物モデルとしてカニクイザルが有用であることを示すことができた。また、サルに対する体外循環カラムの実験系も確立できた。不妊と疼痛を主訴とする子宮内膜症の新規治療法の確立のための土台作りは本研究課題で達成できた。これらは少子・晩婚化の現在に社会的意義のある基礎研究となりえたと考えられる。

Research Products

• [Journal Article] Endometrial Immunity for Embryo Implantation and Pregnancy Establishment (2020)
  • Author(s): Kitazawa Jun、Kimura Fuminori、Nakamura Akiko、Morimune Aina、Takahashi Akimasa、Takashima Akiko、Amano Tsukuru、Tsuji Shunichiro、Kaku Shoji、Kasahara Kyoko、Murakami Takashi
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 250 Issue: 1 Pages: 49-60
  • DOI: 10.1620/tjem.250.49
  • NAID: 130007790947
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] Review: Chronic endometritis and its effect on reproduction. (2019)
  • Author(s): Kimura F, Takebayashi A, Ishida M, Nakamura A, Kitazawa J, Morimune A, Hirata K, Takahashi A, Tsuji S, Takashima A, Amano T, Tsuji S, Ono T, Kaku S, Kasahara K, Moritani S, Kushima R, Murakami T.
  • Journal Title: J Obstet Gynaecol Res. Volume: 45 Issue: 5 Pages: 951-960
  • DOI: 10.1111/jog.13937
  • Peer Reviewed / Open Access
• [Journal Article] Increased mast cells in endocervical smears of women with dysmenorrhea (2018)
  • Author(s): Tsuji Shunichiro, Tsuji Kiyoshi, Otuska Hirokuni, Murakami Takashi
  • Journal Title: Cytojournal Volume: 15 Pages: 1-4
  • DOI: 10.4103/cytojournal.cytojournal_54_17
  • NAID: 120006539737
  • Peer Reviewed / Open Access