Development of a new induction method for differentiation, morphological direct reprogramming

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21904
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Morita Yasuyuki 熊本大学, 大学院先端科学研究部(工), 教授 (90380534)
• Co-Investigator(Kenkyū-buntansha): 小俣 誠二 熊本大学, 大学院先端科学研究部(工), 助教 (60624814)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: ダイレクトリプログラミング / 再生医療 / マイクロパターニング

Outline of Final Research Achievements

We paid attention to cellular morphology as a new technology for direct reprogramming. It means that we discussed about the potential of cellular alteration from a cell of the body into the other cell of the body by controlling the cellular morphology. We tried to change from a fibroblast (start cell) into an astrocyte (targeting cell) through the morphological direct reprogramming. The expression of GFAP, which is a differentiation marker of astrocyte, was observed from human dermal fibroblasts who were seeded on the astrocyte-formed cellular adherence micropatterns. This result suggests that the characteristics of start cells could be changed into the one of targeting cells just by controlling the cellular morphology.

Free Research Field

バイオメカニクス

Academic Significance and Societal Importance of the Research Achievements

ダイレクトリプログラミングは，幹細胞へ戻す初期化プロセスを経ないため，初期化プロセスを経る分化誘導法と比して効率が約10倍増加する．しかし既存のダイレクトリプログラミング手法は，体細胞をiPS細胞へ戻す初期化プロセスと基本的に同じ遺伝子導入法を用いている．そのため，プロセス数は軽減されるが，発がん化リスクおよびコストの問題などは解決されていない．本研究で得られた成果は，既存の再生・細胞医療の繁雑なプロセスを劇的に簡略化させるとともに，そこに内包されるがん化リスク，コスト問題を克服する可能性を秘めている．