Generation of functional insulin-producing cells from mouse embryonic stem cells through 804G cell-derived extracellular matrix and protein transduction of transcription factors

Taku Kaitsuka, Hirofumi Noguchi, Nobuaki Shiraki, Takuya Kubo, Fan Yan Wei, Farzana Hakim, Shoen Kume, Kazuhito Tomizawa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Embryonic stem (ES) and induced pluripotent stem (iPS) cells have potential applications to regenerative medicine for diabetes; however, a useful and safe way to generate pancreatic β cells has not been developed. In this study, we tried to establish an effective method of differentiation through the protein transduction of three transcription factors (Pdx1, NeuroD, and MafA) important to pancreatic β cell development. The method poses no risk of unexpected genetic modifications in target cells. Transduction of the three proteins induced the differentiation of mouse ES and mouse iPS cells into insulin-producing cells. Furthermore, a laminin-5-rich extracellular matrix efficiently induced differentiation under feeder-free conditions. Cell differentiation was confirmed with the expression of the insulin 1 gene in addition to marker genes in pancreatic β cells, the differentiated cells secreted glucose-responsive C-peptide, and their transplantation restored normoglycemia in diabetic mice. Moreover, Pdx1 protein transduction had facilitative effects on differentiation into pancreatic endocrine progenitors from human iPS cells. These results suggest the direct delivery of recombinant proteins and treatment with laminin-5-rich extracellular matrix to be useful for the generation of insulinproducing cells.

Original languageEnglish
Pages (from-to)114-127
Number of pages14
JournalStem Cells Translational Medicine
Volume3
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • Diabetes
  • Embryonic stem cells
  • Induced pluripotent stem cells
  • Pancreatic differentiation
  • Transcription factors

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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