Induction of Expandable Adipose-Derived Mesenchymal Stem Cells from Aged Mesenchymal Stem Cells by a Synthetic Self-Replicationg RNA.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10435
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: University of the Ryukyus
• Principal Investigator: Shiohira Chika 琉球大学, 医学(系)研究科(研究院), 助教 (50325833)
• Co-Investigator(Kenkyū-buntansha): 野口 洋文 琉球大学, 医学(系)研究科(研究院), 教授 (50378733)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: iTS-M cells / iPS cells / reprogramming factors / ADSCs / VEE-RNA vector

Outline of Final Research Achievements

ADSCs have attracted attention due to their potential for use in the treatment of various diseases. However, the self-renewal capacity of ADSCs is restricted and their function diminishes during passage. We generated induced tissue-specific Mesenchymal(hiTS-M)Stem cells from human aged ADSCs deficient in self-renewal, to use a single synthetic self-replicating Venezuelan Equine Encephalitis (VEE)-reprogramming factor (RF) RNA replicon (SR-RNA) expressing the reprogramming factors OCT4, KLF4,SOX2, and GLIS1. These hiTS-M cells transfected with the SR-RNA vector survived for 15 passages. The hiTS-M cells expressed cell surface markers similar to those of hADSCs and differentiated into fat cells and osteoblasts. Global gene expression profiling showed that hiTS-Mcells were transcriptionally similar to hADSCs. These data suggest that the generation of iTS cells has important implications for the clinical application of autologous stem cell transplantation.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

脂肪由来幹細胞(ADSCs)は、脂肪・骨・軟骨などの中胚葉系細胞への分化が可能な点や多くの成長因子を分泌することで臓器・組織の修復を促す点により、様々な疾患の治療に使用できる可能性を秘めた細胞として近年注目、多くの臨床研究の報告がなされている。しかしADSCsの自己複製能は限定的で、継代数を重ねることによる機能低下が報告されている。本研究は老化して自己複製能を失ったヒトADSCsにiPS作成技術を応用してヒト人工間葉系幹細胞(iTS-M細胞)を樹立した点が独創的であり、臨床応用を考慮した場合、ADSCsの安定供給およびバンク化を目指すうえで、本研究は臨床応用の実現性の高い研究であると思われる。