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Directed differentiation of human iPSC into insulin producing cells is improved by induced expression of PDX1 and NKX6.1 factors in IPC progenitors.
Walczak, Maciej P; Drozd, Anna M; Stoczynska-Fidelus, Ewelina; Rieske, Piotr; Grzela, Dawid P.
Afiliación
  • Walczak MP; Department of Research and Development, Celther Polska Ltd., Milionowa 23, 93-193, Lódz, Poland.
  • Drozd AM; Department of Research and Development, Celther Polska Ltd., Milionowa 23, 93-193, Lódz, Poland.
  • Stoczynska-Fidelus E; Department of Research and Development, Celther Polska Ltd., Milionowa 23, 93-193, Lódz, Poland.
  • Rieske P; Department of Tumor Biology, Medical University of Lódz, Zeligowskiego 7/9, 90-752, Lódz, Poland.
  • Grzela DP; Department of Research and Development, Celther Polska Ltd., Milionowa 23, 93-193, Lódz, Poland.
J Transl Med ; 14(1): 341, 2016 12 20.
Article en En | MEDLINE | ID: mdl-27998294
BACKGROUND: Induced pluripotent stem cells (iPSC) possess an enormous potential as both, scientific and therapeutic tools. Their application in the regenerative medicine provides new treatment opportunities for numerous diseases, including type 1 diabetes. In this work we aimed to derive insulin producing cells (IPC) from iPS cells established in defined conditions. METHODS: We optimized iPSC generation protocol and created pluripotent cell lines with stably integrated PDX1 and NKX6.1 transgenes under the transcriptional control of doxycycline-inducible promoter. These cells were differentiated using small chemical molecules and recombinant Activin A in the sequential process through the definitive endoderm, pancreatic progenitor cells and insulin producing cells. Efficiency of the procedure was assessed by quantitative gene expression measurements, immunocytochemical stainings and functional assays for insulin secretion. RESULTS: Generated cells displayed molecular markers characteristic for respective steps of the differentiation. The obtained IPC secreted insulin and produced C-peptide with significantly higher hormone release level in case of the combined expression of PDX1 and NKX6.1 induced at the last stage of the differentiation. CONCLUSIONS: Efficiency of differentiation of iPSC to IPC can be increased by concurrent expression of PDX1 and NKX6.1 during progenitor cells maturation. Protocols established in our study allow for iPSC generation and derivation of IPC in chemically defined conditions free from animal-derived components, which is of the utmost importance in the light of their prospective applications in the field of regenerative medicine.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Transactivadores / Proteínas de Homeodominio / Células Secretoras de Insulina / Células Madre Pluripotentes Inducidas Tipo de estudio: Guideline Límite: Animals / Humans Idioma: En Revista: J Transl Med Año: 2016 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Transactivadores / Proteínas de Homeodominio / Células Secretoras de Insulina / Células Madre Pluripotentes Inducidas Tipo de estudio: Guideline Límite: Animals / Humans Idioma: En Revista: J Transl Med Año: 2016 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Reino Unido