Development of predictive markers to analyze the differentiation potentials of bone marrow-derived mesenchymal stromal cells

• Project/Area Number: 17K11541
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Plastic surgery
• Research Institution: Hiroshima University
• Principal Investigator: KANAWA MASAMI 広島大学, 自然科学研究支援開発センター, 助教 (00284208)
• Co-Investigator(Kenkyū-buntansha): 藤本 勝巳 広島大学, 医系科学研究科(歯), 助教 (40294566) ; 平田 伊佐雄 広島大学, 医系科学研究科(歯), 助教 (40346507) ; 河本 健 広島大学, 学術・社会連携室, 特任教授 (50224861)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 間葉系幹細胞 / 分化予知マーカー / 骨分化 / 軟骨分化 / 脂肪分化 / 遺伝子発現 / 線維芽細胞 / 移植・再生医療 / ITGA5

Outline of Final Research Achievements

We identified differentiation-predicting marker genes for bone marrow-derived mesenchymal stromal cells (MSCs). We analyzed the correlation between the gene levels of MSCs before and after induction of differentiation (osteogenic, chondrogenic, and adipogenic). MSCs can have different differentiation directions and potentials depending on the source; therefore, we confirmed the marker genes that reflect these differences among significantly correlated genes. We selected 15, 11, and 8 predictive markers for osteogenic, adipogenic, and chondrogenic differentiation, respectively. These genes were divided into three groups with different potentials: one lineage, two lineages with osteogenic and adipogenic or adipogenic and chondrogenic, and three lineages. Our results suggest that these genes will be useful in examining the differentiation potential of MSCs before induction.

Academic Significance and Societal Importance of the Research Achievements

研究対象に用いたMSCは、癌化のリスクがiPS細胞より低いこと、ES細胞と比較して倫理面で利用しやすいこと、培養が容易であるなど多数の利点を有している。さらにMSCは骨、軟骨、脂肪などへの分化能を有しており、再生医療に既に応用されている。しかしMSCの分化能は株によって分化の方向性あり、分化レベルも一定ではない。そこで臨床応用を成功させるためには、MSCの分化能を予測することが必要である。しかし、分化能を予測する方法については不明な点が多く確立されていない。本研究で得られた結果は、MSCの分化能を事前に把握するための一手段として再生医療に寄与すると考えられる。

Research Products

• [Int'l Joint Research] AIRLANGGA UNIVERSITY(インドネシア)
• [Int'l Joint Research] Universitas Airlangga(インドネシア)
• [Journal Article] The Identification of Marker Genes for Predicting the Osteogenic Differentiation Potential of Mesenchymal Stromal Cells (2021)
  • Author(s): Kanawa Masami、Igarashi Akira、Fujimoto Katsumi、Saskianti Tania、Nakashima Ayumu、Higashi Yukihito、Kurihara Hidemi、Kato Yukio、Kawamoto Takeshi
  • Journal Title: Current Issues in Molecular Biology Volume: 43 Issue: 3 Pages: 2157-2166
  • DOI: 10.3390/cimb43030150
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Potential Marker Genes for Predicting Adipogenic Differentiation of Mesenchymal Stromal Cells (2019)
  • Author(s): Masami Kanawa, Akira Igarashi, Katsumi Fujimoto, Veronica Sainik Ronald, Yukihito Higashi, Hidemi Kurihara, Yukio Kato, Takeshi Kawamoto
  • Journal Title: Applied Sciences Volume: 9 Issue: 14 Pages: 1-9
  • DOI: 10.3390/app9142942
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic Markers Can Predict Chondrogenic Differentiation Potential in Bone Marrow-Derived Mesenchymal Stromal Cells (2018)
  • Author(s): Kanawa M, Igarashi A, Fujimoto K, Higashi Y, Kurihara H, Sugiyama M, Saskianti T, Kato Y, Kawamoto T
  • Journal Title: Stem Cells International Volume: 10 Pages: 1-9
  • DOI: 10.1155/2018/9530932
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum-Free Medium Enhances the Immunosuppressive and Antifibrotic Abilities of Mesenchymal Stem Cells Utilized in Experimental Renal Fibrosis (2018)
  • Author(s): Yoshida K, Nakashima A, Doi S, Ueno T, Okubo T, Kawano KI, Kanawa M, Kato Y, Higashi Y, Masaki T
  • Journal Title: STEM CELLS TRANSLATIONAL MEDICINE Volume: 7 Issue: 12 Pages: 893-905
  • DOI: 10.1002/sctm.17-0284
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of human dental pulp cells grown in chemically defined serum-free medium (2018)
  • Author(s): Fujii S, Fujimoto K, Goto N, Abiko Y, Imaoka A, Shao J, Kitayama K, Kanawa M, Sosiawan A, Suardita K, Nishimura F, Kato Y
  • Journal Title: Biomed Rep Volume: 8(4) Pages: 350358-350358
  • DOI: 10.3892/br.2018.1066
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 骨髄由来間葉系幹細胞（MSC）の骨、軟骨、脂肪分化予知マーカー遺伝子の同定 (2023)
  • Author(s): 金輪真佐美, 五十嵐 晃, 藤本勝巳, Veronica Sainik Ronald, Tania Saskianti, 中島 歩, 東 幸仁, 栗原英見, 加藤幸夫, 河本 健
  • Organizer: 第22回日本再生医療学会総会
• [Presentation] 間葉系幹細胞の骨分化能予知遺伝子マーカーの同定 (2022)
  • Author(s): 金輪真佐美, 五十嵐 晃, 藤本勝巳,Tania Saskianti, 中島 歩, 東 幸仁, 栗原英見, 加藤幸夫, 河本 健
  • Organizer: 第45回日本分子生物学会
• [Presentation] 骨髄由来MSCの脂肪分化予知遺伝子マーカーの同定 (2020)
  • Author(s): 金輪 真佐美、五十嵐 晃、藤本 勝巳、東 幸仁、栗原 英見、加藤 幸夫、河本 健
  • Organizer: 第43回日本分子生物学会年会
• [Presentation] 3D解析による骨髄由来間葉系幹細胞の軟骨分化予知遺伝子マーカーの研究 (2019)
  • Author(s): 金輪真佐美、五十嵐晃、藤本勝巳、東幸仁、栗原英見、杉山勝、加藤幸夫、河本健
  • Organizer: 第42回日本分子生物学会年会