Caracterization of a IRM1 as a Novel Marker for Immortalization of Retinal Pigment Epithelial Cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21642
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry; Ophthalmology
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Kuroda Takuya 国立医薬品食品衛生研究所, 再生・細胞医療製品部, 主任研究官 (70648857)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: iPS細胞 / 網膜色素上皮細胞 / 不死化細胞 / 造腫瘍性細胞

Outline of Final Research Achievements

Human pluripotent stem cells (hPSCs) are leading candidate raw materials for cell-based therapeutic products (CTPs). In the development of hPSC-derived CTPs, it is imperative to ensure that they do not form tumors after transplantation for safety reasons. Because cellular immortalization is a landmark of malignant transformation and a common feature of cancer cells, we aimed to develop an in vitro assay for detecting immortalized cells in CTPs. We employed retinal pigment epithelial (RPE) cells as a model of hPSC-derived products and identified a gene encoding slow skeletal muscle troponin T (TNNT1) as a novel marker of immortalized RPE cells by comprehensive microarray analysis. We demonstrated that TNNT1 mRNA expression is higher in several cancer tissues than in normal tissues. Furthermore, stable expression of TNNT1 in ARPE-19 cells affected actin filament organization and enhanced their migration ability.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

ヒトiPS細胞を用いた再生医療製品の安全性において最も懸念される問題は移植細胞のがん化である。そのため、未分化細胞や目的外細胞の残存を評価する試験法を確立する事が非常に重要である。この試験法では、下方検出限界3%まで正常RPE細胞に混入させた不死化RPE細胞を検出可能であることを示した。また、今回、不死化RPEマーカーTNNT1は、卵巣癌等いくつかのがん組織でも優位に高発現していることを明らかとした。この試験法は、iPS細胞由来移植細胞の品質管理に貢献することが期待される。