Induction of human iTS-P and iTS-L cells using iPS cell technology

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05404
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: University of the Ryukyus
• Principal Investigator: NOGUCHI Hirofumi 琉球大学, 医学(系)研究科(研究院), 教授 (50378733)
• Co-Investigator(Kenkyū-buntansha): 齊藤 一誠 新潟大学, 医歯学系, 准教授 (90404540)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 再生医療 / iTS細胞 / iPS細胞 / 体性幹細胞

Outline of Final Research Achievements

We recently demonstrated the generation of mouse induced tissue-specific stem (iTS) cells through transient overexpression of reprogramming factors combined with tissue-specific selection. Here we induced expandable tissue-specific stem/progenitor (iTS) cells from human pancreatic/hepatic tissue through transient expression of genes encoding the reprogramming factors OCT4, p53 shRNA, SOX2, KLF4, L-MYC, and LIN28.
Transfection of episomal plasmid vectors into human pancreatic tissue efficiently generated iTS cells expressing genetic markers of endoderm and tissue-specific progenitors. The iTS cells differentiated into insulin/albumin-producing cells more efficiently than human iPS cells. iTS cells subcutaneously inoculated into immunodeficient mice did not form teratomas. The generation of human iTS cells may have important implications for the clinical application of stem/progenitor cells.

Free Research Field

細胞移植・再生医療

Academic Significance and Societal Importance of the Research Achievements

本研究により、組織特異的幹細胞を人工的に作製することが可能であることが、ヒト細胞で証明された。この細胞の利点は１）樹立効率がiPS細胞よりも高い、２）分化誘導効率がES/iPS細胞より高い、３）奇形腫形成がなくES/iPS細胞で懸念された未分化細胞残存による腫瘍形成の心配がない、の3点である。この技術は膵・肝のみならず、さまざまな組織に関して応用可能であると考えられるため、画期的な技術であるといえる。今後、臨床応用化へ向けてiTS細胞の有効性・安全性試験を行っていきたい。