Novel therapeutic strategy by intrabone marrow co-transplantation of cord blood and cord-derived mesenchymal stem cells

• Project/Area Number: 16K07185
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Hyogo Medical University
• Principal Investigator: OKADA Masaya 兵庫医科大学, 医学部, 講師 (00309452)
• Co-Investigator(Kenkyū-buntansha): 相馬 俊裕 兵庫医科大学, 医学部, 非常勤講師 (40273619) ; 吉原 哲 兵庫医科大学, 医学部, 講師 (90461037) ; 池亀 和博 兵庫医科大学, 医学部, 講師 (20372609)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 臍帯血移植 / 間葉系幹細胞 / 骨髄内臍帯血移植 / 骨髄内移植 / 生着促進

Outline of Final Research Achievements

We developed an intra bone marrow transplantation (IBMT) of unwashed cord blood method. We carried out a phase I study which showed IBMT of unwashed cord blood with reduced intensity conditioning regimen is safe and well tolerated in adult patients. After that, in order to confirm the improvement of donor engraftment rate, a multicenter phase II trial was conducted. Forty patients with hematologic malignancies were enrolled. Full donor engraftment rate was 86.8%. IBMT of unwashed cord blood increased engraftment rate.

Academic Significance and Societal Importance of the Research Achievements

成人臍帯血移植は難治性造血器腫瘍に対する根治的治療法として行われているが、移植細胞数が骨髄移植の約1/10と少ないため生着不全のリスクが高く、血球回復が遅延するという問題が生じ、移植関連死亡率の悪化をきたす原因となっている。一方、経静脈的に輸注された造血幹細胞の多くは、肺などの臓器にトラップされ、骨髄に到達するものは移植された幹細胞の10%程度であるため、骨髄に直接投与する骨髄内移植法は臍帯血移植の欠点を克服させる可能性がある。研究代表者らは骨髄内臍帯血移植第Ⅰ相試験を行い、輸注の安全性を明らかにした。この骨髄内臍帯血移植術を発展させ、有用性を確認する必要がある。

Research Products

• [Journal Article] Early evaluation of tumor response to 90Y-ibritumomab radioimmunotherapy in relapsed/refractory B cell non-Hodgkin lymphoma: what is the optimal timing for FDG-PET/CT? (2019)
  • Author(s): Kitajima K, Okada M, et al.
  • Journal Title: Eur Radiol. Volume: - Issue: 7 Pages: 3935-3944
  • DOI: 10.1007/s00330-019-06134-7
  • Peer Reviewed
• [Journal Article] Low incidence of HHV‐6 reactivation in haploidentical hematopoietic stem cell transplantation with corticosteroid as graft‐vs‐host disease prophylaxis compared with cord blood transplantation (2019)
  • Author(s): Tamaki Hiroya、Ikegame Kazuhiro、Yoshihara Satoshi、Kaida Katsuji、Yoshihara Kyoko、Inoue Takayuki、Kato Ruri、Nakata Jun、Fujioka Tatsuya、Soma Toshihiro、Okada Masaya、Ogawa Hiroyasu
  • Journal Title: Transplant Infectious Disease Volume: - Issue: 3
  • DOI: 10.1111/tid.13073
  • Peer Reviewed
• [Journal Article] A prospective multicenter phase II study of intrabone marrow transplantation of unwashed cord blood using reduced-intensity conditioning. (2018)
  • Author(s): Okada M, Tasaka T, et al.
  • Journal Title: Eur J Haematol. Volume: 100 Issue: 4 Pages: 335-343
  • DOI: 10.1111/ejh.12999
  • Peer Reviewed
• [Journal Article] Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment (2018)
  • Author(s): Okada M, Imagawa J, et al.
  • Journal Title: Clin Lymphoma Myeloma Leuk. Volume: 18 Issue: 5 Pages: 353-360
  • DOI: 10.1016/j.clml.2018.03.004
  • NAID: 120006463738
  • Peer Reviewed / Open Access
• [Journal Article] 急性GVHD・クローン病に対する羊膜由来間葉系幹細胞の医師主導治験 －兵庫医科大学発・初認定ベンチャーによる開発をめざして－ (2018)
  • Author(s): 山原 研一, 濱田 彰子, 大西 俊介, 相馬 俊裕, 岡本 里香, 中村 志郎, 岡田 昌也, 吉原 哲, 吉原 享子, 橋本 大吾, 磯江 敏幸, 豊嶋 崇徳, 佐藤 典宏, 藤盛 好啓
  • Journal Title: 兵庫医科大学医学会雑誌 Volume: 43 Pages: 41-45
  • Peer Reviewed
• [Journal Article] Spousal hematopoietic stem cell transplantation. (2017)
  • Author(s): Ikegame K, Okada M et al.,
  • Journal Title: International Jounal of Hematol. Volume: 105 Issue: 5 Pages: 645-657
  • DOI: 10.1007/s12185-016-2168-y
  • Peer Reviewed
• [Journal Article] Bone marrow-derived mesenchymal stem cells (JR-031) for steroid-refractory grade III or IV acute graft-versus-host disease: a phase II/III study. (2016)
  • Author(s): Muroi K, Miyamura K, Okada M, Yamashita T, Murata M, Ishikawa T, Uike N, Hidaka M, Kobayashi R, Imamura M, Tanaka J, Ohashi K, Taniguchi S, Ikeda T, Eto T, Mori M, Yamaoka M, Ozawa K.
  • Journal Title: Int J Hematol Volume: 103 Issue: 2 Pages: 243-250
  • DOI: 10.1007/s12185-015-1915-9
  • Peer Reviewed
• [Journal Article] Host Foxp3+CD4+ Regulatory T Cells Act as a Negative Regulator of Dendritic Cells in the Peritransplantation Period. (2016)
  • Author(s): Inoue T. (5) Fujimori Y. (2)
  • Journal Title: J.immunol. Volume: 196 Issue: 1 Pages: 469-483
  • DOI: 10.4049/jimmunol.1402950
  • Peer Reviewed / Open Access
• [Presentation] The efficacy of mesenchymal stem cells for the treatment of steroid-refractory acute GVHD (2018)
  • Author(s): 福永 景子, 池亀 和博, 海田 勝仁, 井上 貴之, 吉原 哲, 吉原 享子, 大杉 夕子, 玉置 広哉, 岡田 昌也, 小川 啓恭, 藤盛 好啓
  • Organizer: 日本血液学会総会
• [Presentation] 2018158714 間葉系幹細胞(MSC)によるステロイド抵抗性急性移植片対宿主病(SR-aGVHD)治療 (2018)
  • Author(s): 岡田昌也
  • Organizer: 日本輸血・細胞治療学会近畿支部総会
  • Invited
• [Presentation] 間葉系幹細胞(MSC)によるステロイド抵抗性急性移植片対宿主病(SR-aGVHD)治療 (2017)
  • Author(s): 岡田昌也
  • Organizer: 第61回日本輸血・細胞治療学会近畿支部総会
  • Invited
• [Presentation] 骨髄間葉系幹細胞による急性GVHD治療 (2016)
  • Author(s): 岡田昌也
  • Organizer: 第105回近畿血液学地方会
  • Place of Presentation: テイジンホール(大阪府大阪市）