Development of hybrid corneal tissue transplantation technology using stem cells via genome reprogramming

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11332
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Teikyo University (2017-2018); Tokyo Women's Medical University (2016)
• Principal Investigator: Mimura Tatsuya 帝京大学, 医学部, 准教授 (70463867)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 角膜 / 幹細胞 / メチル化

Outline of Final Research Achievements

The purpose of this study is to examine the changes involved in the aging of cells in the cornea. Tissue stem cells from corneal layers were collected by sphere method. We examined the gene expression of stem cells and found that genes such as Nestin, which is a marker for undifferentiated nervous system, were highly expressed. Examination of the methylation of these cells demonstrated a high degree of methylation as compared to normal cultured cells. We could obtained daughter cells, which were high quality cells without shortening the telomere length or without staining with βGAL, from stem cells. We transplanted the regenerated cornea into an rabbit eyes. Transplanted cornea maintained transparency postoperatively. These results suggests that the transplanted undifferentiated cells may be a source of cell proliferation after transplantation.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

培養細胞を移植する報告は各臓器において、研究レベルあるいは臨床レベルで行われている。しかし、移植後に、生着し、そして細胞の供給源にする技術は確立されていなかった。我々が採取した組織幹細胞から得られた前駆細胞は未分化な状態を維持し、しかも動物眼に移植した後も細胞の供給源となり、角膜透明性維持に働いた。分子・遺伝子レベルでは、テロメア長が短縮せず、DNAのメチル化率が低い状態の細胞であることが分かった。本技術を使うことにより、自己の細胞群から選択的に質の良い細胞を採取し、更に自己に戻ることにより疲弊した組織を修復が可能となることが示唆された。また本方法は他の臓器にも応用可能というメリットもある。