Functional regulation and producion for next-generation of mesenchymal stem cells

• Project/Area Number: 16K10376
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Yamagata University
• Principal Investigator: Tajima Katsushi 山形大学, 医学部, 非常勤講師 (80292423)
• Co-Investigator(Kenkyū-buntansha): 富山 健一 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 薬物依存研究部, 科研費研究員 (20584064) ; 滝澤 和也 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, 研究員(任非) (20739388) ; 安田 武嗣 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, 主任研究員(定常) (60332269) ; 小原 千寿香 (逸見千寿香) 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, 主任研究員(任非) (90415977)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 間葉系幹細胞 / 放射線障害 / 再生医療 / 相同組み換え / mesenchyma stem cells / iPSCs / RAD52 / double-strand breaks / homologous recombination / acetylation / double-strand break / deacetylation / mesenchymal stem cell / PAI-1 / vitronectin / furin / iPS / MSC / 医学放射線生物学

Outline of Final Research Achievements

The generation of induced-pluripotential stem cells (iPSCs)-derived mesenchymal stem cells (iMSCs) is an attractive and promising approach for preparing large, uniform batches of applicable MSCs that can serve as an alternative cell source of primary MSCs. Appropriate culture surfaces may influence their growth and differentiation potentials during iMSC derivation. In the present study, we established the simple and effective derivation method for mouse iMSCs using extracellular component as gelatin.
The iMSCs provide with several biological activities including protecting radiation-exposure cells. The mouse iMSCs established by this method can be used as a tool for to precisely analyzing anti-inflammatory or immunoregulatory roles of MSCs in a congenic mouse models, in addition to serving as an alternative cell source of primary MSCs and an off-the-shelf product.

Academic Significance and Societal Importance of the Research Achievements

間葉系幹細胞（MSC）は多分化能、抗炎症作用、血管新生、組織損傷部位へのホーミング等の生物活性を示すことから、放射線障害をはじめとした様々な病態の細胞治療ソースとして注目を集めてきた。一方、由来組織（骨髄、脂肪、臍帯）、培養条件により分泌因子の産生性や選択性が制限されることも知られている。これらの理由により、個々の研究の正確な比較を困難にしてきた。また投与されたMSC が、期待された効果を示さず反対の作用を示すこともあり、臨床応用上、問題となっていた。本研究では、iPS細胞から人為的にMSCを誘導することで、生物活性を自在に制御できる次世代型の間葉系幹細胞の創生した。

Research Products

• [Journal Article] Giant cellulitis-like Sweet syndrome as an initial clinical presentation of acute myeloblastic leukemia with t(6;9)(p23;q34): DEK-CAN and internal duplications of FMS-like tyrosine kinase 3 (2019)
  • Author(s): Okuyama Shuhei、Nito Toshiya、Yanagawa Naoki、Tajima Katsushi
  • Journal Title: Annals of Hematology Volume: 98 Issue: 3 Pages: 787-788
  • DOI: 10.1007/s00277-019-03613-1
  • Peer Reviewed
• [Journal Article] MultiSite Gateway Technology Is Useful for Donor DNA Plasmid Construction in CRISPR/Cas9-Mediated Knock-In System (2018)
  • Author(s): Yasuda Takeshi、Tajima Katsushi
  • Journal Title: IntechOpen Volume: 2 Pages: 1-21
  • Peer Reviewed / Open Access
• [Journal Article] Nocardia otitidiscaviarum meningitis in a diffuse large B-cell lymphoma patient with CD4-positive lymphocytopenia and persistent oligoclonal CD8-positive lymphocytes in the peripheral blood (2018)
  • Author(s): Katsushi Tajima, Taichi Terada, Shuhei Okuyama, Daisuke Akaneya, Ryuichiro Hori, Shuichi Abe, Mitsumasa Osakabe, Hiroaki Kumagai1, Riko Tsumanuma1, Eijiro Omoto, Junko Ito6, Tohru Gonoi
  • Journal Title: Int J Clin Exp Pathol Volume: 11 Pages: 455-461
  • Peer Reviewed / Open Access
• [Journal Article] Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites (2018)
  • Author(s): Yasuda Takeshi、Kagawa Wataru、Tajima Katsushi
  • Journal Title: PLOS Genetics Volume: 14 Issue: 3 Pages: 1007277-1007277
  • DOI: 10.1371/journal.pgen.1007277
  • NAID: 120006459820
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epstein-Barr virus clonality and plasmacytosis in a patient with atypical angioimmunoblastic T cell lymphoma (2017)
  • Author(s): Okuyama Shuhei、Terada Taichi、Kumagai Hiroaki、Tsumanuma Riko、Omoto Eijiro、Ueki Tetsuya、Yanagawa Naoki、Maeda Kunihiko、Tajima Katsushi
  • Journal Title: Annals of Hematology Volume: 97 Issue: 3 Pages: 537-539
  • DOI: 10.1007/s00277-017-3189-1
  • Peer Reviewed
• [Journal Article] Pseudo-grey platelet syndrome in a pregnant patient (2017)
  • Author(s): Tanaka Kiwa、Moriya Mika、Hasegawa Tsuyoshi、Okuyama Shuhei、Ueki Tetsuya、Tajima Katsushi
  • Journal Title: British Journal of Haematology Volume: 178 Issue: 6 Pages: 836-836
  • DOI: 10.1111/bjh.14808
  • Peer Reviewed
• [Journal Article] Differentiation and Molecular Properties of Mesenchymal Stem Cells Derived from Murine Induced Pluripotent Stem Cells Derived on Gelatin or Collagen (2016)
  • Author(s): Obara C, Takizawa K, Tomiyama K, Hazawa M, Saotome-Nakamura A, Gotoh T, Yasuda T, Tajima K
  • Journal Title: Stem cells international Volume: - Issue: 1 Pages: 9013089-9013089
  • DOI: 10.1155/2016/9013089
  • Peer Reviewed / Open Access
• [Journal Article] Intra- and extracellular plasminogen activator inhibitor-1 regulate effect of vitronectin against radiation-induced endothelial cell death (2016)
  • Author(s): Hazawa M, Yasuda T, Saotome-Nakamura A, Tomiyama K, Obara C, Gotoh T, Tajima K
  • Journal Title: Vascular Pharmacology Volume: 87 Pages: 150-158
  • DOI: 10.1016/j.vph.2016.09.006
  • Peer Reviewed