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FOXO3-Engineered Human ESC-Derived Vascular Cells Promote Vascular Protection and Regeneration.
Yan, Pengze; Li, Qingqing; Wang, Lixia; Lu, Ping; Suzuki, Keiichiro; Liu, Zunpeng; Lei, Jinghui; Li, Wei; He, Xiaojuan; Wang, Si; Ding, Jianjian; Chan, Piu; Zhang, Weiqi; Song, Moshi; Izpisua Belmonte, Juan Carlos; Qu, Jing; Tang, Fuchou; Liu, Guang-Hui.
Afiliação
  • Yan P; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;
  • Li Q; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, College of Life Sciences, Peking University, Beijing 100871, China.
  • Wang L; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
  • Lu P; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, College of Life Sciences, Peking University, Beijing 100871, China.
  • Suzuki K; Institute for Advanced Co-Creation Studies, Graduate School of Engineering Science, Osaka University, Osaka 560-8531, Japan; Graduate School of Engineering Science, Osaka University, Osaka 560-8531, Japan.
  • Liu Z; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
  • Lei J; Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China.
  • Li W; Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China.
  • He X; Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China.
  • Wang S; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Ding J; Army Diagnosis and Treatment Center for Oral Disease, 306th Hospital of the PLA, Beijing 100101, China.
  • Chan P; Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China.
  • Zhang W; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Advanced Innovation Center for Human Brain Protection, National
  • Song M; University of the Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
  • Izpisua Belmonte JC; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Qu J; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. El
  • Tang F; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, College of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Ministry of Education Key Laboratory of Cell Proliferat
  • Liu GH; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Advanced Innovation Center for Human Brain Protection, National
Cell Stem Cell ; 24(3): 447-461.e8, 2019 03 07.
Article em En | MEDLINE | ID: mdl-30661960
ABSTRACT
FOXO3 is an evolutionarily conserved transcription factor that has been linked to longevity. Here we wanted to find out whether human vascular cells could be functionally enhanced by engineering them to express an activated form of FOXO3. This was accomplished via genome editing at two nucleotides in human embryonic stem cells, followed by differentiation into a range of vascular cell types. FOXO3-activated vascular cells exhibited delayed aging and increased resistance to oxidative injury compared with wild-type cells. When tested in a therapeutic context, FOXO3-enhanced vascular cells promoted vascular regeneration in a mouse model of ischemic injury and were resistant to tumorigenic transformation both in vitro and in vivo. Mechanistically, constitutively active FOXO3 conferred cytoprotection by transcriptionally downregulating CSRP1. Taken together, our findings provide mechanistic insights into FOXO3-mediated vascular protection and indicate that FOXO3 activation may provide a means for generating more effective and safe biomaterials for cell replacement therapies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regeneração / Engenharia Genética / Células Endoteliais / Células-Tronco Embrionárias / Proteína Forkhead Box O3 Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regeneração / Engenharia Genética / Células Endoteliais / Células-Tronco Embrionárias / Proteína Forkhead Box O3 Idioma: En Ano de publicação: 2019 Tipo de documento: Article