Development of comprehensive cellular therapy for acute and late-onset radiation-induced injuries

• Project/Area Number: 26293277
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Hiroshima University
• Principal Investigator: Tatsuo Ichinohe 広島大学, 原爆放射線医科学研究所, 教授 (80314219)
• Co-Investigator(Kenkyū-buntansha): 三浦 康生 京都大学, 医学(系)研究科(研究院), 助教 (70605146) ; 前川 平 京都大学, 医学(系)研究科(研究院), 教授 (80229286)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 被ばく医療 / 組織再生治療 / 造血細胞移植 / 間葉系幹細胞

Outline of Final Research Achievements

In this study, we aimed to develop comprehensive cellular therapy for acute syndrome and late effects associated with radiation-induced tissue/organ injuries by use of differential regenerative functions of hematopoietic stem cells (HSCs) and mesenchymal stem/stromal cells (MSCs). We found that dual transplantation of HSCs and MSCs ameliorates skin and large bowel injuries associated with acute radiation exposure and graft-versus-host disease compared with transplant of HSCs alone in an irradiated (8 Gy) mouse model. Intriguingly, such protective effect was reproducible in mice receiving HSCs with culture supernatant of MSCs instead of MSCs themselves. We also established a unique method to efficiently isolate MSCs from human umbilical cord blood for the future MSC banking system free from invasive procedures to the donors .

Research Products

• [Journal Article] Bortezomib interferes with adhesion of B cell precursor acute lymphoblastic leukemia cells through SPARC up-regulation in human bone marrow mesenchymal stromal/stem cells. (2017)
  • Author(s): Iwasa M, Miura Y, Fujishiro A, Fujii S, Sugino N, Yoshioka S, Yokota A, Hishita T, Hirai H, Andoh A, Ichinohe T, Maekawa T.
  • Journal Title: Int J Hematol. Volume: 105 Issue: 5 Pages: 587-597
  • DOI: 10.1007/s12185-016-2169-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Isolation of mesenchymal stromal/stem cells from cryopreserved umbilical cord blood cells (2017)
  • Author(s): Fujii S, Miura Y, Iwasa M, Yoshioka S, Fujishiro A, Sugino N, Kaneko H, Nakagawa Y, Hirai H, Takaori-Kondo A, Ichinohe T, Maekawa T.
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 57 Issue: 1 Pages: 1-8
  • DOI: 10.3960/jslrt.16019
  • NAID: 130005709558
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pharmacological targeting of bone marrow mesenchymal stromal/stem cells for the treatment of hematological disorders. (2017)
  • Author(s): Sugino N, Ichinohe T, Takaori-Kondo A, Maekawa T, Miura Y.
  • Journal Title: Inflammation and Regeneration. Volume: - Issue: 1 Pages: 1-7
  • DOI: 10.1186/s41232-017-0038-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles. (2016)
  • Author(s): Sugino N, #Miura Y, Yao H, Iwasa M, Fujishiro A, Fujii S, Hirai, Takaori-Kondo A, Ichinohe T, Maekawa T (#Corresponding author).
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 469 Issue: 4 Pages: 823-829
  • DOI: 10.1016/j.bbrc.2015.12.061
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Isolation of mesenchymal stromal/stem cells from small-volume umbilical cord blood units that do not qualify for the banking system. (2015)
  • Author(s): Yoshioka S, #Miura Y, Iwasa M, Fujishiro A, Yao H, Miura M, Fukuoka M, Nakagawa Y, Yokota A, Hirai H, Ichinohe T, Takaori-Kondo A, Maekawa T (#Corresponding author).
  • Journal Title: International Journal of Hematology Volume: 102 Issue: 2 Pages: 218-229
  • DOI: 10.1007/s12185-015-1828-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Human Mesenchymal Stromal/Stem Cell-Mediated Bone Marrow Organization. (2015)
  • Author(s): Miura Y, Ichinohe T, Maekawa T.
  • Journal Title: 日本輸血細胞治療学会誌 Volume: 61 Pages: 489-490
  • NAID: 130005103552
  • Peer Reviewed
• [Journal Article] The impact of HLA mismatch direction on the outcome of unrelated bone marrow transplantation: A retrospective analysis from the JSHCT. (2015)
  • Author(s): Kanda J, Ichinohe T, Fuji S, Maeda Y, Ohashi K, Fukuda T, Miyamura K, Iwato K, Eto T, Hirohisa Nakamae H, Kobayashi N, Mori T, Mori SI, Morishima Y, Atsuta Y, Kanda Y
  • Journal Title: Biol Blood Marrow Transplant Volume: 21 Issue: 2 Pages: 305-11
  • DOI: 10.1016/j.bbmt.2014.10.015
  • Peer Reviewed / Open Access
• [Journal Article] Biological significance of HLA locus matching in unrelated donor bone marrow transplantation. (2015)
  • Author(s): Morishima Y, Kashiwase K, Matsuo K, Azuma F, Morishima S, Onizuka M, Yabe T, Murata M, Doki N, Eto T, Mori T, Miyamura K, Sao H, Ichinohe T, Saji H, Kato S, Atsuta Y, Kawa K, Kodera Y, Sasazuki T; Japan Marrow Donor Program.
  • Journal Title: Blood Volume: 125 Issue: 7 Pages: 1189-1197
  • DOI: 10.1182/blood-2014-10-604785
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Impact of conditioning intensity and total body irradiation on acute graft-versus-host disease after hematopoietic cell transplantation. (2015)
  • Author(s): Nakasone N, Fukuda T, Kanda J, Mori T, Yano S, Kobayashi T, Miyamura K, Eto T, Kanamori H, Iwato K, Uchida N, Mori SI, Nagamura-Inoue T, Ichinohe T, Atsuta Y, Teshima T, Murata M.
  • Journal Title: Bone Marrow Transplant Volume: 50 Issue: 4 Pages: 559-65
  • DOI: 10.1038/bmt.2014.293
  • Peer Reviewed / Open Access
• [Journal Article] CCR1-mediated Accumulation of Myeloid Cells in the Liver Microenvironment Promoting Mouse Colon Cancer Metastasis (2014)
  • Author(s): Hirai H, et al
  • Journal Title: Clinical and Experimental Metastasis Volume: 32 Issue: 8 Pages: 2245-55
  • DOI: 10.1002/stem.1701
  • Peer Reviewed / Open Access
• [Journal Article] 移植合併症への系統的アプローチ (2014)
  • Author(s): 一戸辰夫
  • Journal Title: 臨床血液 Volume: 55 Pages: 2125-35
  • NAID: 130004696107
  • Peer Reviewed / Open Access
• [Presentation] Effects of acute exposure to low-dose radiateon on the characteristics of human bone marrow mesenchymal stromal/stem cells. (2017)
  • Author(s): Aya Fujishiro, Yasuo Miura, Sumie Fujii, Tatsuo Ichinohe.
  • Organizer: The 1st International Symposium of the network-type Joint Usage/Research Center for Radiation Disaster Medical Science-Scientific Underpinning for Restoration from a Radiation Diaster
  • Place of Presentation: 広島市
  • Year and Date: 2017-02-21
  • Int'l Joint Research
• [Presentation] Late Adherent Subpopulation in Umbilical Cord Blood Has the Same Characteristics and Hematopoiesis-Supporting Capacity As Mesenchymal Stromal/Stem Cells. (2016)
  • Author(s): Satoshi Yoshioka, Yasuo Miura, Masaki Iwasa, Aya Fujishiro, Noriko Sugino, Sumie Fujii, Yoko Nakagawa, Atsushi Sato, Asumi Yokota, Hideyo Hirai, Tatsuo Ichinohe, Akifumi-Kondo Takaori, Taira Maekawa.
  • Organizer: 58th Annual Meeting & Exposition of the American Society of Hematology
  • Place of Presentation: San Diego, CA, U.S.A.
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] 低線量放射線が間葉系幹細胞の機能に与える影響. (2016)
  • Author(s): 藤城綾, 三浦康生, 岩佐麿佐紀, 藤井紀恵, 杉野典子, 安藤朗, 前川平, 一戸辰夫.
  • Organizer: 日本放射線影響学会第59回大会
  • Place of Presentation: 広島市
  • Year and Date: 2016-10-28
• [Presentation] 高線量被ばく事故に対する救援治療の新たな可能性. (2016)
  • Author(s): 一戸辰夫.
  • Organizer: 日本放射線影響学会第59回大会
  • Place of Presentation: 広島市
  • Year and Date: 2016-10-27
  • Invited
• [Presentation] Vitamin K2 supports hematopoiesis through acting on human bone marrow mesenchymal stromal/stem cells. (2016)
  • Author(s): Aya Fujishiro, Yasuo Miura, Masaki Iwasa, Sumie Fujii, Noriko Sugino, Atsushi Sato, Asumi Yokota, Hideyo Hirai, Akira Andoh, Kaoru Tohyama, Tatsuo Ichinohe, Taira Maekawa.
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-10-14
• [Presentation] Human bone marrow mesenchymal stromal/stem cells modulate IMiDs-induced differentiation of HSPCs. (2016)
  • Author(s): Sumie Fuji, Yasuo Miura, Masaki Iwasa, Aya Fujishiro, Noriko Sugino, Atsushi Sato, Asumi Yokota, Hideyo, Hirai, Akifumi Takaori-Kondo, Tatsuo Ichinohe, Taira Maekawa.
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-10-13
• [Presentation] さい帯血バンクの保存基準に満たない少容量さい帯血からの間葉系幹細胞の分離. (2016)
  • Author(s): 吉岡聡, 三浦康生, 岩佐麿佐紀, 藤城綾, 藤井紀恵, 杉野典子, 平位秀世, 一戸辰夫, 高折晃史, 前川平.
  • Organizer: 第38回日本造血細胞移植学会総会.
  • Place of Presentation: 名古屋市
  • Year and Date: 2016-03-04
• [Presentation] Bortezomib attenuates adhesion of B-cell precursor acture lymphoblastic leukemia cells to bone marrow mesenchymal stromal/stem cells via regulating SPARC expression. (2015)
  • Author(s): Masaki Iwasa, Yasuo Miura, Aya Fujishiro, Sumie Fujii, Noriko Sugino, Satoshi Yoshioka, Akihiro Tamura, Atsushi Sato, Asumi Yokota, Katsuyuki Kito, Akira Ando, Hideyo Hirai, Akifumi Takaori-Kondo, Tatsuo Ichinohe, Taira Maekawa.
  • Organizer: 57th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Orlando, FL
  • Year and Date: 2015-12-07
  • Int'l Joint Research
• [Presentation] Vitamin K2 Supports Hematopoiesis through Acting on Bone Marrow Mesenchymal Stromal/Stem Cells. (2015)
  • Author(s): Aya Fujishiro, Yasuo Miura, Masaki Iwasa, Sumie Fujii, Akihiro Tamura, Atsushi Sato, Asumi Yokota, Noriko Sugino, Hideyo Hirai, Akira Ando, Tatsuo Ichinohe, Taira Maekawa.
  • Organizer: 57th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Orlando, FL
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] Actually delivered dose in total-body irradiation is widely heterogenous depending on the anatomical site. (2015)
  • Author(s): Kumi Oshima, Masahiro Kenjo, Yasushi Nagata, Tatsuo Ichinohe.
  • Organizer: The 20th Annual Congress of Asia-Pacific Blood and Marrow Transplantation Group
  • Place of Presentation: 名護市
  • Year and Date: 2015-11-01
  • Int'l Joint Research
• [Presentation] Effects of low-dose irradiation on the function of human bone marrow mesenchymal stromal/stem cells. (2015)
  • Author(s): Aya Fujishiro, Yasuo Miura, Masaki Iwasa, Akihiro Tamura, Atsushi Sato, Asumi Yokota, Hideyo Hirai, Akira Ando, Taira Maekawa, Tatsuo Ichinohe.
  • Organizer: 第77回日本血液学会学術集会.
  • Place of Presentation: 金沢市
  • Year and Date: 2015-10-17
• [Presentation] Recent advancement in stem cell transplantation for casualties of nuclear disaster. (2015)
  • Author(s): Tatsuo Ichinohe.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: 京都市
  • Year and Date: 2015-05-27
  • Int'l Joint Research / Invited
• [Presentation] 放射線照射が骨髄間葉系幹細胞の機能に与える影響. (2015)
  • Author(s): 岩佐麿佐紀, 三浦康生, 藤城綾, 吉岡聡, 田村彰広, 佐藤淳至, 横田明日美, 平位秀世, 安藤朗, 一戸辰夫, 前川平
  • Organizer: 第37回日本造血細胞移植学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-06
• [Presentation] Effects of irradiation on the functional characteristics of human bone marrow mesenchymal stromal/stem cells. (2014)
  • Author(s): Iwasa M, Miura Y, Fujishiro A, Tamura A, Sato A, Yokota A, Nakagawa Y, Yoshioka S, Hirai H, Andoh A, Ichinohe T, Maekawa T.
  • Organizer: 56th Annual Meeting of the American Society for Hematology
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2014-12-06
• [Presentation] Effects of irradiation on the characteristics of human bone marrow mesenchymal stromal/stem cells (2014)
  • Author(s): Masaki Iwasa, Yasuo Miura, Hisayuki Yao, Satoshi Yoshioka, Aya Fujishiro, Akihiro Tamura, Atsushi Sato, Asumi Yokota, Hideyo Hirai, Akira Ando, Tatsuo Ichinohe, Taira Maekawa
  • Organizer: 第76回日本血液学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Isolation of mesenchymal stromal/stem cells from UCB ineligible for public UCB donation (2014)
  • Author(s): Satoshi Yoshioka, Yasuo Miura, Hisayuki Yao, Masaki Iwasa, Aya Fujishiro, Yayoi Higashi, Asumi Yokota, Akihiro Tamura, Atsushi Sato, Hideyo Hirai, Tatsuo Ichinohe, Akifumi Takaori-Kondo, Taira Maekawa
  • Organizer: 第76回日本血液学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Differential impact of HLA matching on outcomes of unrelated marrow and cord blood transplantation. (2014)
  • Author(s): Ichinohe T
  • Organizer: 19th Annual Summer Meeting of the Korean Society of Blood and Marrow Transplantation.
  • Place of Presentation: Busan, Korea
  • Year and Date: 2014-08-29
  • Invited
• [Remarks] 原爆放射線医科学研究所 研究・教員紹介 血液・腫瘍内科
  • URL: http://home.hiroshima-u.ac.jp/hematol/research-activities.html
• [Remarks] 広島大学原爆放射線医科学研究所 血液・腫瘍内科研究分野 研究紹介
  • URL: https://www.hiroshima-u.ac.jp/rbm/research/lab/Hematology_and_Oncology