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Improved hematopoietic differentiation of primate embryonic stem cells by inhibition of the PI3K-AKT pathway under defined conditions.
Nii, Takenobu; Marumoto, Tomotoshi; Kohara, Hiroshi; Yamaguchi, Saori; Kawano, Hirotaka; Sasaki, Erika; Kametani, Yoshie; Tani, Kenzaburo.
Afiliação
  • Nii T; Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  • Marumoto T; Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  • Kohara H; Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Project Division of ALA Advanced Medical Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Yamaguchi S; Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  • Kawano H; Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  • Sasaki E; Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
  • Kametani Y; Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
  • Tani K; Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Project Division of ALA Advanced Medical Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Electronic address: k-tani
Exp Hematol ; 43(10): 901-911.e4, 2015 Oct.
Article em En | MEDLINE | ID: mdl-26073521
Hematopoietic stem/progenitor cells (HSPCs) derived from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have potential therapeutic applications in humans. To assess the safety and efficacy of ESC/iPSC-based therapies, reliable animal models are required prior to their clinical application. The common marmoset (CM) was recently found to be a useful nonhuman primate animal model for drug development and safety assessment. However, a method for the efficient hematopoietic differentiation of CM ESCs has not been established. In this study, we developed a novel and efficient method for differentiating CM ESCs into hematopoietic cells by transiently inhibiting the phosphoinositide 3-kinase (PI3K)-Protein kinase B (AKT) pathway, a critical pathway that maintains the undifferentiated state of CM ESCs during embryoid body (EB) formation. Compared with controls, transient inhibition of the P13K-AKT pathway resulted in a threefold increase in the proportion of enriched CD34⁺ cells (p < 0.001) and an increase in the number of hematopoietic colonies on day 8 of CM EB cultures. Moreover, number of blast colonies, number of hematopoietic progenitor cell populations of CD34⁺CD117⁺, CD34⁺CD45⁺, and CD43⁺CD45⁺ cells, and expression of hematopoietic genes were increased by transient inhibition of the PI3K-AKT pathway. We also demonstrated that the hematopoietic progenitor cell population was increased by inhibition of PI3K in a human system. Our novel and efficient ESC differentiation method might be useful for preclinical research on human hematopoietic disorders and may be efficiently translated to human ESC/iPSC-based regenerative medicine.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Fosfatidilinositol 3-Quinases / Proteínas Proto-Oncogênicas c-akt / Células-Tronco Embrionárias / Hematopoese Tipo de estudo: Guideline Limite: Animals / Humans Idioma: En Revista: Exp Hematol Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Fosfatidilinositol 3-Quinases / Proteínas Proto-Oncogênicas c-akt / Células-Tronco Embrionárias / Hematopoese Tipo de estudo: Guideline Limite: Animals / Humans Idioma: En Revista: Exp Hematol Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Japão