A novel mechanism of posttransplant female infertiliy

• Project/Area Number: 25670443
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Hokkaido University
• Principal Investigator: TESHIMA TAKANORI 北海道大学, 医学(系)研究科(研究院), 教授 (40284096)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 造血幹細胞移植 / GVHD / 卵巣 / 不妊 / 免疫抑制剤

Outline of Final Research Achievements

Infertility associated with ovarian failure is a serious late complication for female survivors of allogeneic hematopoietic stem cell transplantation (allo-SCT). We have addressed whether GVHD could impact female fertility in murine models of allo-SCT.　Our results demonstrate for the first time that GVHD induces infertility by targeting the granulosa cells in the ovaries and GVHD prevention could preserve ovarian functions. These results have important clinical implications in young female transplant recipients with nonmalignant diseases, where minimally toxic chemotherapies prior to SCT and conditioning regimen were used.

Research Products

• [Journal Article] Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning. (2014)
  • Author(s): Koyama M, Hashimoto D, Nagafuji K, Eto T, Ohno Y, Aoyama K, Iwasaki H, Miyamoto T, Hill GR, Akashi K, Teshima T.
  • Journal Title: Bone Marrow Transplant. Volume: 2014 Issue: 1 Pages: 110-115
  • DOI: 10.1038/bmt.2013.134
  • NAID: 120005460247
  • Peer Reviewed / Open Access
• [Journal Article] Mammalian target of rapamycin inhibitors permit regulatory T cell reconstitution and inhibit experimental chronic graft-versus-host disease. (2014)
  • Author(s): Sugiyama H, Maeda Y, Nishimori H, Yamasuji Y, Matsuoka K, Fjii N, Kondo E, Shinagawa K, Takeuchi K, Teshima T, and Tanimoto M
  • Journal Title: Biol Blood Marrow Transplant. Volume: 20 Issue: 2 Pages: 183-91
  • DOI: 10.1016/j.bbmt.2013.11.018
  • NAID: 120005469526
  • Peer Reviewed / Open Access
• [Journal Article] Bone Marrow Graft-versus-Host Disease: Evaluation of Its Clinical Impact on Disrupted Hematopoiesis after Allogeneic Hematopoietic Stem Cell Transplantation (2014)
  • Author(s): Souichi Shiratori, Mizuha Kosugi-Kanaya, Satoshi Ueha, Junichi Sugita1, Akio Shigematsu, Takeshi Kondo, Daigo Hashimoto, Katsuya Fujimoto, Tomoyuki Endo, Mitsufumi Nishio, Satoshi Hashino, Yoshihiro Matsuno, Kouji Matsushima, Junji Tanaka, Masahiro Imamura, Takanori Teshima
  • Journal Title: Biol Blood Marrow Transplant Volume: 20 Issue: 4 Pages: 495-500
  • DOI: 10.1016/j.bbmt.2013.12.568
  • NAID: 120005427744
  • Peer Reviewed / Open Access
• [Journal Article] Stenotrophomonas maltophilia infection during allogeneic hematopoietic stem cell transplantation: a single-center experience (2014)
  • Author(s): Shiratori S, Wakasa K, Okada K, Sugita J, Akizawa K, Shigematsu A, Hashimoto D, Fujimoto K, Endo T, Kondo T, Shimizu C, Hashino S, Teshima T
  • Journal Title: Clin Transplant Volume: 28(6) Issue: 6 Pages: 656-661
  • DOI: 10.1111/ctr.12356
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] High Level of Serum Soluble Interleukin-2 Receptor at Transplantation Predicts Poor Outcome of Allogeneic Stem Cell Transplantation for Adult T Cell Leukemia. (2014)
  • Author(s): Shigematsu A, Kobayashi N, Yasui H, Shindo M, Kakinoki Y, Koda K, Iyama S, Kuroda H, Tsutsumi Y, Imamura M, Teshima T.
  • Journal Title: Biol Blood Marrow Transplant Volume: － Issue: 6 Pages: 801-805
  • DOI: 10.1016/j.bbmt.2014.02.014
  • NAID: 120005455889
  • Peer Reviewed / Open Access
• [Journal Article] The Use of Oral Beclomethasone Dipropionate in the Treatment of Gastrointestinal Graft-versus-host Disease: The Experience of the Fukuoka Blood and Marrow Transplantation (BMT) Group (2014)
  • Author(s): Takashima S, Eto T, Shiratsuchi M, Hidaka M, Mori Y, Kato K, Kamezaki K, Oku S, Henzan H, Takase K, Matsushima T, Takenaka K, Iwasaki H, Miyamoto T, Akashi K, Teshima T
  • Journal Title: Internal Medicine Volume: 53 Issue: 12 Pages: 1315-1320
  • DOI: 10.2169/internalmedicine.53.1858
  • NAID: 130004466355
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Essential requirements for setting up a stem cell processing laboratory (2014)
  • Author(s): Leemhuis T, Padley D, Keever-Taylor C, Niederwieser D, Teshima T, Lanza F, Chabannon C, Szabolcs P, Bazarbachi A, Koh MB
  • Journal Title: Bone Marrow Transplant Volume: 49(8) Issue: 8 Pages: 1098-1105
  • DOI: 10.1038/bmt.2014.104
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning for mycosis fungoides and Sezary syndrome. (2014)
  • Author(s): Shiratori S, Fujimoto K, Nishimura M, Hatanaka KC, Kosugi-Kanaya M, Okada K, Sugita J, Shigematsu A, Hashimoto D, Endo T, Kondo T, Abe R, Hashino S, Matsuno Y, Shimizu H, Teshima T.
  • Journal Title: Hematol Oncol Volume: Epub Ahead of Print Issue: 1 Pages: 9-16
  • DOI: 10.1002/hon.2162
  • NAID: 120005981361
  • Peer Reviewed / Open Access
• [Journal Article] Hepatitis B virus (HBV) reverse seroconversion (RS) can be prevented even in non-responders to hepatitis B vaccine after allogeneic stem cell transplantation: long-term analysis of intervention in RS with vaccine for patients with previous HBV infection (2014)
  • Author(s): Takahata M, Hashino S, Onozawa M, Shigematsu A, Sugita J, Fujimoto K, Endo T, Kondo T, Tanaka J, Imamura M, Teshima T
  • Journal Title: Transpl Infect Dis Volume: 16(5) Issue: 5 Pages: 797-801
  • DOI: 10.1111/tid.12283
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] JAK inhibitors: a home run for GVHD patients? (2014)
  • Author(s): Teshima T
  • Journal Title: Blood Volume: 123(24) Issue: 24 Pages: 3691-3693
  • DOI: 10.1182/blood-2014-04-570325
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Quantification of hematogones at the time of engraftment is a useful prognostic indicator in allogeneic stem cell transplantation. (2013)
  • Author(s): Shima T
  • Journal Title: Blood Volume: 121 Issue: 5 Pages: 840-848
  • DOI: 10.1182/blood-2012-02-409607
  • Peer Reviewed
• [Journal Article] A novel filtration method for cord blood processing using a polyester fabric filter (2013)
  • Author(s): Shima T, Forraz N, Sato N, Yamauchi T, Iwasaki H, Takenaka K, Akashi K, McGuckin C, Teshima T
  • Journal Title: Int J Lab Hematol Volume: 35 Issue: 4 Pages: 436-446
  • DOI: 10.1111/ijlh.12039
  • Peer Reviewed
• [Journal Article] Evaluation of the feasibility and efficacy of autologous stem cell transplantation in elderly patients with multiple myeloma. (2013)
  • Author(s): Muta T, Miyamoto T, Fujisaki T, Ohno Y, Kamimura T, Kato K, Takenaka K, Iwasaki H, Eto T, Takamatsu Y, Teshima T, Akashi K
  • Journal Title: Intern Med Volume: 52(1) Pages: 63-70
  • NAID: 130003365558
  • Peer Reviewed
• [Journal Article] Decrease in Venous Irritation by Adjusting the Concentration of Injected Bendamustine (2013)
  • Author(s): Watanabe H, Ikesue H, Tsujikawa T, Nagata K, Uchida M, Suetsugu K, Egashira N, Muta T, Kato K, Takenaka K, Ohga S, Matsushima T, Shiratsuchi M, Miyamoto T, Teshima T, Akashi K, Oishi R
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 36 Issue: 4 Pages: 574-578
  • DOI: 10.1248/bpb.b12-00901
  • NAID: 130003361397
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Diagnosis and evaluation of intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation following reduced-intensity and myeloablative conditioning regimens (2013)
  • Author(s): Yamasaki S, Miyagi-Maeshima A, Kakugawa Y, Matsuno Y, Ohara-Waki F, Fuji S, Morita-Hoshi Y, Mori M, Kim S, Mori S, Fukuda T, Tanosaki R, Shimono T, Tobinai K, Saito D, Takaue Y, Teshima T, Heike Y
  • Journal Title: Int J Hematol Volume: 97(3) Issue: 3 Pages: 421-426
  • DOI: 10.1007/s12185-013-1297-9
  • NAID: 10031162908
  • Peer Reviewed
• [Journal Article] Protective roles of epithelial cells in the survival of adult T-cell leukemia/lymphoma cells. (2013)
  • Author(s): Miyatake Yukiko
  • Journal Title: The American Journal of Pathology Volume: 182 Issue: 5 Pages: 1832-1842
  • DOI: 10.1016/j.ajpath.2013.01.015
  • Peer Reviewed
• [Journal Article] Evaluating the association between histological manifestations of cord colitis syndrome with GVHD. (2013)
  • Author(s): Shimoji S, Kato K, Eriguchi Y, Takenaka K, Iwasaki H, Miyamoto T, Oda Y, Akashi K, Teshima T
  • Journal Title: Bone Marrow Transplant Volume: 48 Issue: 9 Pages: 1249-1252
  • DOI: 10.1038/bmt.2013.44
  • Peer Reviewed
• [Journal Article] Autologous peripheral blood stem cell transplantation with granulocyte colony-stimulating factor combined conditioning regimen as a postremission therapy for acute myelogenous leukemia in first complete remission (2013)
  • Author(s): Eto T, Takase K, Miyamoto T, Ohno Y, Kamimura T, Nagafuji K, Takamatsu Y, Teshima T, Gondo H, Taniguchi S, Akashi K, Harada M
  • Journal Title: Int J Hematol Volume: 98 Issue: 2 Pages: 186-196
  • DOI: 10.1007/s12185-013-1378-9
  • NAID: 10031194734
  • Peer Reviewed
• [Journal Article] Unrelated allogeneic bone marrow-derived mesenchymal stem cells for steroid-refractory acute graft-versus-host disease: a phase I/II study. (2013)
  • Author(s): Muroi K, Miyamura K, Ohashi K, Murata M, Eto T, Kobayashi N, Taniguchi S, Imamura M, Ando K, Kato S, Mori T, Teshima T, Mori M, Ozawa K.
  • Journal Title: Int J Hematol. Volume: 98 Issue: 2 Pages: 206-213
  • DOI: 10.1007/s12185-013-1399-4
  • NAID: 10031194736
  • Peer Reviewed
• [Journal Article] Combination of high-dose melphalan and bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma. (2013)
  • Author(s): Miyamoto T, Yoshimoto G, Kamimura T, Muta T, Takashima S, Ito Y, Shiratsuchi M, Choi I, Kato K, Takenaka K, Iwasaki H, Takamatsu Y, Teshima T, Akashi K.
  • Journal Title: Int J Hematol Volume: 98 Issue: 3 Pages: 337-345
  • DOI: 10.1007/s12185-013-1402-0
  • Peer Reviewed
• [Journal Article] Inhibiting retinoic acid signaling ameliorates graft-versus-host disease by modifying T-cell differentiation and intestinal migration (2013)
  • Author(s): Aoyama K, Saha A, Tolar J, Riddle MJ, Veenstra RG, Taylor PA, Blomhoff R, Panoskaltsis-Mortari A, Klebanoff CA, Socie G, Munn DH, Murphy WJ, Serody JS, Fulton L, Teshima T, Chandraratna RA, Dmitrovsky E, Guo Y, Noelle RJ, Blazar BR
  • Journal Title: Blood Volume: 122(12) Issue: 12 Pages: 2125-2134
  • DOI: 10.1182/blood-2012-11-470252
  • Peer Reviewed
• [Journal Article] Reciprocal expression of enteric antimicrobial proteins in intestinal graft-versus-host disease. (2013)
  • Author(s): Eriguchi Y, Uryu H, Nakamura K, Shimoji S, Takashima S, Iwasaki H, Miyamoto T, Shimono N, Hashimoto D, Akashi K, Ayabe T, Teshima T.
  • Journal Title: Biol Blood Marrow Transplant Volume: 19 Issue: 10 Pages: 1525-1529
  • DOI: 10.1016/j.bbmt.2013.07.027
  • NAID: 120005347004
  • Peer Reviewed
• [Journal Article] Clinical outcomes of allogeneic stem cell transplantation for relapsed or refractory follicular lymphoma: a retrospective analysis by the Fukuoka Blood and Marrow Transplantation Group. (2013)
  • Author(s): 107 Ito Y, Miyamoto T, Kamimura T, Takase K, Henzan H, Sugio Y, Kato K, Ohno Y, Eto T, Teshima T, Akashi K
  • Journal Title: Int J Hematol Volume: 98 Issue: 4 Pages: 463-471
  • DOI: 10.1007/s12185-013-1430-9
  • Peer Reviewed
• [Presentation] Graft-Versus-Host Disease Targets Granulosa Cell of Ovarian Follicle and Causes Infertility after Allogeneic Hematopoietic Stem Cell Transplantation (2015)
  • Author(s): Shimoji S, Hashimoto D, Kato K, Tujigiwa H, Akashi K, Teshima T
  • Organizer: 2015 BMT Tandem Meetings
  • Place of Presentation: Manchester Grand Hyatt(San Diego USA)
  • Year and Date: 2015-02-11 – 2015-02-15
• [Presentation] 同種造血幹細胞移植後の不妊 (2014)
  • Author(s): 下地 園子, 加藤 光次, 辻極 秀次, 江里口 芳裕, 瓜生 英尚, 髙嶋 秀一郎, 橋本 大吾, 宮本 敏浩, 岩崎 浩己, 赤司 浩一, 豊嶋 崇徳
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪府・大阪市)
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Key players in intestinal GVHD (2014)
  • Author(s): 橋本 大吾, 豊嶋 崇徳
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪府・大阪市)
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Mechanisms of intestinal and pulmonary GVHD after allogeneic stem cell transplantation (2014)
  • Author(s): Teshima T
  • Organizer: Kolloquium 2014 Hematology and Oncology
  • Place of Presentation: Freiburg University(Freiburg, Germany)
  • Year and Date: 2014-06-30
  • Invited
• [Presentation] Role of the intestinal tract for acute GVHD (2014)
  • Author(s): Teshima T
  • Organizer: Kolloquium 2014 Immunity and Infection
  • Place of Presentation: Freiburg University(Freiburg, Germany)
  • Year and Date: 2014-06-30
  • Invited
• [Presentation] Graft-Versus-Host Disease Targets Ovary and Causes Infertility After Allogeneic Hematopoietic Stem Cell Transplantation (2013)
  • Author(s): Shimoji S, Kato K, Tsujigiwa H, Eriguchi Y, Lee L, Uryu H, Takashima S, Hashimoto D, Akashi K and Teshima T
  • Organizer: ASH 2013
  • Place of Presentation: Ernest N. Morial Convention Center(USA)