Study for mesenchymal stem cells derived from the two different origin

• Project/Area Number: 18K06264
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Kumamoto University
• Principal Investigator: Era Takumi 熊本大学, 発生医学研究所, 教授 (00273706)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 間葉系幹細胞 / 細胞由来

Outline of Final Research Achievements

Mesenchymal stem cells (MSCs) isolated from adult human tissues are capable of proliferating in vitro and maintaining their multipotency, making them attractive cell sources for regenerative medicine. However, the availability and capability of self-renewal under current preparation regimes are limited. Induced pluripotent stem cells (iPSCs) now offers an alternative, similar cell source to MSCs. Herein, we established new methods for differentiating hiPSCs into MSCs via mesoderm-like and neuroepithelium-like cells. Both derived MSC populations exhibited self-renewal and multipotency, as well as therapeutic potentials in mouse models of skin wounds, pressure ulcers, and osteoarthritis. Interestingly, the therapeutic effects differ between the two types of MSCs in the disease models, suggesting that the therapeutic effect depends on the cell origin. Our results provide valuable basic insights for the clinical application of such cells.

Academic Significance and Societal Importance of the Research Achievements

この研究成果は、iPS細胞由来MSCの臨床での治療効果の基盤的知見となる。また個体からMSCと採取することにかわり、iPS細胞から同一的なMSCを将来誘導、分離、増幅するために役立つ知見となる。

Research Products

• [Journal Article] Novel Drug Candidates Improve Ganglioside Accumulation and Neural Dysfunction in GM1 Gangliosidosis Models with Autophagy Activation (2020)
  • Author(s): Ryutaro Kajihara, Tadahiro Numakawa, Haruki Odaka, Yuji Yaginuma, Noemi Fusaki, Toshika Okumiya, Hirokazu Furuya, Seiji Inui, and Takumi Era
  • Journal Title: Stem Cell Reports Volume: 14 Issue: 5 Pages: 1-15
  • DOI: 10.1016/j.stemcr.2020.03.012
  • Peer Reviewed / Open Access
• [Journal Article] Presynaptic Dysfunction in Neurons Derived from Tay-Sachs iPSCs. (2019)
  • Author(s): Matsushita K, Numakawa T, Odaka H, Kajihara R, Soga M, Ozasa S, Nakamura K, Mizuta H and Era T.
  • Journal Title: Neuroscience Volume: 414 Pages: 128-140
  • DOI: 10.1016/j.neuroscience.2019.06.026
  • Peer Reviewed
• [Journal Article] Activin Is Superior to BMP7 for Efficient Maintenance of Human iPSC-Derived Nephron Progenitors. (2019)
  • Author(s): Tanigawa S, Naganuma H, Kaku Y, Era T, Sakuma T, Yamamoto T, Taguchi A and Nishinakamura R.
  • Journal Title: Stem Cell Reports Volume: 13 Issue: 2 Pages: 322-337
  • DOI: 10.1016/j.stemcr.2019.07.003
  • Peer Reviewed / Open Access
• [Journal Article] Simplifying the Chemical Structure of Cationic Lipids for siRNA-Lipid Nanoparticles. (2019)
  • Author(s): Kuboyama T, Yagi K, Naoi T, Era T, Yagi N, Nakasato Y, Yabuuchi H, Takahashi S, Shinohara F, Iwai H, Koubara-Yamada A, Hasegawa K, Miwa A.
  • Journal Title: ACS Med Chem Lett. Volume: 10 Issue: 5 Pages: 749-753
  • DOI: 10.1021/acsmedchemlett.8b00652
  • Peer Reviewed
• [Journal Article] Mesenchymal Stem Cells Derived from Human iPS Cells via Mesoderm and Neuroepithelium Have Different Features and Therapeutic Potentials. (2018)
  • Author(s): Eto S, Goto M, Soga M, Kaneko Y, Uehara Y, Mizuta H and Era T
  • Journal Title: PLos One Volume: 13 Issue: 7 Pages: e0200790-e0200790
  • DOI: 10.1371/journal.pone.0200790
  • Peer Reviewed
• [Journal Article] Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency (2018)
  • Author(s): Ito Naofumi、Katoh Kaoru、Kushige Hiroko、Saito Yutaka、Umemoto Terumasa、Matsuzaki Yu、Kiyonari Hiroshi、Kobayashi Daiki、Soga Minami、Era Takumi、Araki Norie、Furuta Yasuhide、Suda Toshio、Kida Yasuyuki、Ohta Kunimasa
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1634-1634
  • DOI: 10.1038/s41598-018-20057-1
  • Peer Reviewed / Open Access
• [Journal Article] Tracing the destiny of mesenchymal stem cells from embryo to adult bone marrow and white adipose tissue via Pdgfr expression. (2018)
  • Author(s): Miwa H and Era T
  • Journal Title: Development Volume: 145 Issue: 2 Pages: 2-2
  • DOI: 10.1242/dev.155879
  • Peer Reviewed
• [Presentation] Deviation and differentiation in mesenchymal stem cell. (2020)
  • Author(s): Takumi Era
  • Organizer: 第53回日本発生生物学会年会
• [Presentation] Presynaptic dysfunction in neurons derived from Tay-Sachs-iPSCs. (2020)
  • Author(s): Takumi Era, Kozo Matsushita, Ryutaro Kajihara, Haruki Odaka, Minami Soga, Kimitoshi Nakamura and Tadahiro Numakawa.
  • Organizer: 16th Annual WORLD Symposium
  • Int'l Joint Research
• [Presentation] Derivation, Induction and Gene manipulation in Mesenchymal Stem Cell. (2019)
  • Author(s): Takumi Era
  • Organizer: The 25th Annual Meeting of Japan Society of Gene and Cell Therapy.
  • Invited
• [Presentation] 疾患由来iPS細胞を使った疾患解析と薬剤開発 (2019)
  • Author(s): 江良択実
  • Organizer: 第67回日本輸血・細胞治療学会学術総会
  • Invited
• [Presentation] 間葉系幹細胞の起源と分化 (2018)
  • Author(s): 江良 択実
  • Organizer: 第4回幹細胞研究会
  • Invited
• [Presentation] 間葉系細胞の発生と分化 (2018)
  • Author(s): 江良 択実
  • Organizer: 第8回細胞再生医療研究会
  • Invited
• [Presentation] Origin and development of mesenchymal stem cells. (2018)
  • Author(s): Takumi Era
  • Organizer: The 24th Annual Meeting of Japan Society of Gene and Cell Therapy
  • Invited