The novel cell therapy for neuroblastoma by engineered stem cell
| Project/Area Number |
15H05000
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
田尻 達郎 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80304806)
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| Co-Investigator(Kenkyū-buntansha) |
松田 修 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00271164)
東 真弓 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10380453)
文野 誠久 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40405254)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Granted (Fiscal Year 2018)
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| Budget Amount *help |
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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| Keywords | 癌 / 神経芽腫 / 細胞治療 / 分化誘導 / 間葉系幹細胞 / 医療・福祉 |
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| Outline of Annual Research Achievements |
難治性神経芽腫に対する新規治療法として間葉系幹細胞（MSC）および神経幹細胞（NSC）を利
用したEngineered stem cell による分化誘導治療を主とした新規細胞療法の樹立を目的とする。そのために，神経芽腫発生モデルマウス (MYCN-TgM)に対する間葉系幹細胞（MSC）のhoming効果と分化誘導による抗腫瘍効果について検討を行っている．
現在は，ヒト→マウスのxenograftによる免疫応答の要因を排除し，よりhomingについての解析をすすめるためにhomograftであるマウス由来間葉系幹細胞(mMSC) を用いて検証を行っており，MSC腹腔内投与による腫瘍内へのhomingを検証できた．
また,NSCソースとして，未熟奇形腫に着目し，神経幹細胞用培地で腫瘍組織を培養することで，神経細胞スフィアを作成することができ，またその細胞群の仲に神経堤細胞様集団があることも確認できた．今後これらの神経幹細胞を用いることで，容易にengineered stem cellを作成できるかを検証する．
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
神経幹細胞作成に難渋しており，方法論を変更したため
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| Strategy for Future Research Activity |
MYCN抑制miRNA産るMSC（eMSC）および未熟奇形腫由来神経堤幹細胞（NSC）の作成および神経芽腫培養細胞への効果の解析
①Engineered MSC (eMSC)を神経芽腫細胞と共培養させ、神経芽腫細胞におけるMYCN発現の抑制効果を解析する。さらにeMSCの神経芽腫細胞への遊走能、抗腫瘍効果の解析を行う。
②MSC、NSC、eMSCにレチノイン酸を併用した際の神経芽腫培養細胞分化への効果の解析を行う．レチノイン酸を用いて、神経芽腫培養細胞SK-N-SHに分化誘導を行い、この作用がMSC、iNSC、eMSC の存在下で増強されるか、また、その機序に関して解析を行う。
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Report
(3 results)
Research Products
(41 results)
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[Journal Article] Efficient direct conversion of human fibroblasts into myogenic lineage induced by co-transduction with MYCL and MYOD12017
Author(s)
Wakao J, Kishida T, Fumino S, Kimura K, Yamamoto K, Kotani SI, Mizushima K, Naito Y, Yoshikawa T, Tajiri T, Mazda O
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 488
Pages: 368-373
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] JNK-STAT3 pathway in neuroblastoma.2016
Author(s)
Higashi M, Sakai K, Fumino S, Aoi S, Furukawa T, Tajiri T
Organizer
40th World Congress of the International College of Surgeons
Place of Presentation
京都
Year and Date
2016-10-24
Related Report
Int'l Joint Research
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[Presentation] A phase II study of bold delayed local control strategy in children with high risk neuroblastoma: Japan neuroblastoma study group (JN-H-11) trial.2016
Author(s)
Shichino H, Mugishima H, Matsumoto K, Hishiki T, Iehara T, Yoneda A, Soejima T, Takimoto T, Takahashi H, Teramukai S, Kamijo T, Nakazawa A, Fukushima T, Hosoi H, Tajiri T, Nakagawara A
Organizer
48th Congress of the International Society of Paediatric Oncology (SIOP)
Place of Presentation
Dublin, Ireland.
Year and Date
2016-10-19
Related Report
Int'l Joint Research
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[Presentation] Primary tumor resection after high dose chemotherapy with autologous hematopoietic stem cell transplantation is a safe and feasible option. A report from the Japanese Neuroblastoma Study Group (JNBSG).2016
Author(s)
Hishiki T, Yoneda A, Kuroda T, Tokiwa K, Ise K, Ono S, Kinoshita Y, Uehara S, Matsumoto K, Kumagai M, Shichino H, Soejima T, Takimoto T, Hara J, Tajiri T, Nakagawara A
Organizer
Advances in Neuroblastoma Research (ANR)
Place of Presentation
Queensland, Australia.
Year and Date
2016-06-19
Related Report
Int'l Joint Research
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[Presentation] Genomic characterization of high-risk neuroblastoma in Japan: A retrospective study of 537 cases by using updated follow-up data based on INRG variables [Japan Neuroblastoma Study Group (JNBSG)].2016
Author(s)
Ohira M, Kamijo T, Takimoto T, Nakazawa A, Matsumoto K, Shichino H, Hishiki T, Iehara T, Nakamura Y, Nagase H, Yoneda A, Fukushima T, Tajiri T, Nakagawara A
Organizer
Advances in Neuroblastoma Research (ANR)
Place of Presentation
Queensland, Australia.
Year and Date
2016-06-19
Related Report
Int'l Joint Research
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[Presentation] Tumor-homing effect of human mesenchymal stem cells in a TH-MYCN mouse model of neuroblastoma.2016
Author(s)
Kimura K, Kishida T, Wakao J, Tanaka T, Higashi M, Fumino S, Aoi S, Furukawa T, Mazda O, Tajiri T
Organizer
49th Annual Meeting of the Pacific Association of Pediatric Surgeons (PAPS)
Place of Presentation
Kauai, USA
Year and Date
2016-05-17
Related Report
Int'l Joint Research
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