2023 Fiscal Year Final Research Report

Development of gene therapy for PTEN abnormal Cowden syndrome using serum-free iPS cells

Research Project

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Project/Area Number	20K10117
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57060:Surgical dentistry-related
Research Institution	Hiroshima University
Principal Investigator	Kanda Taku 広島大学, 医系科学研究科(歯), 専門研究員 (00423369)
Co-Investigator(Kenkyū-buntansha)	山崎佐知子広島大学, 病院(歯), 病院助教 (00632001) 大林史誠広島大学, 病院(歯), 歯科診療医 (20806096) 濱田充子広島大学, 病院(歯), 助教 (30760318) 岡本哲治東亜大学, その他の研究科, 教授 (00169153) 柳本惣市広島大学, 医系科学研究科(歯), 教授 (10315260)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	Cowden症候群 / iPS細胞 / がん抑制遺伝子
Outline of Final Research Achievements	Peripheral blood lymphocytes from Cowden syndrome patients were collected and heterozygous mutations in the PTEN gene were identified, including replacement of codon 341 Phenylalanine with Leucine and codon 343 Valine with stop codon. We established Cowden disease-specific iPS cell induction by Sendai virus vector in a serum-free culture system that can maintain the undifferentiated nature and multipotent differentiation ability of human ES cells in serum-free medium. Compared to healthy PBMCs and iPS cells, both CS-derived PBMCs and CS-iPSCs showed significantly decreased expression of PTEN transcripts. Translated with DeepL.com (free version)
Free Research Field	口腔外科
Academic Significance and Societal Importance of the Research Achievements	無血清培養系iPS細胞を用いたPTEN異常Cowden症候群の新規原因遺伝子変異を報告した。同遺伝子変異を無血清培地hESF9にてヒトES細胞の継代培養,ヒトiPS細胞における未分化性と多分化能を維持可能な無血清培養系にてセンダイウイルスベクターによるCowden疾患特異性iPS細胞誘導を樹立した。本培養系を応用することでCowden症候群の発症機序の検索、新規治療法の開発を期待できる。