Chemically defined conditions for long-term maintenance of pancreatic progenitors derived from human induced pluripotent stem cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Shuhei Konagaya, Hiroo Iwata

ABSTRACT

Large numbers of hormone-releasing cells, approximately 109 endocrine cells, are required to treat type I diabetes patients by cell transplantation. The SOX9-positive pancreatic epithelium proliferates extensively during the early stages of pancreatic development. SOX9-positive pancreatic epithelium is thought to be an expandable cell source of β cells for transplantation therapy. In this study, we attempted to expand pancreatic progenitors (PPs: PDX1+/SOX9+) derived from four human iPSC lines in three-dimensional (3D) culture using a chemically defined medium and examined the potential of the derived PPs to differentiate into β-like cells. PPs from four human iPSC lines were maintained and effectively proliferated in a chemically defined medium containing epidermal growth factor and R-spondin-1, CHIR99021, fibroblast growth factor-7, and SB431542. PPs derived from one iPSC line can be expanded by more than 104-fold in chemically defined medium containing two of the fives, epidermal growth factor and R-spondin-1. The expanded PPs were also stable following cryopreservation. After freezing and thawing, the PPs proliferated without a decrease in the rate. PPs obtained after 50 days of culture successfully differentiated into insulin-positive β-like cells, glucagon-positive α-like cells, and somatostatin-positive δ-like cells. The differentiation efficiency of expanded PPs was similar to that of PPs without expansion culture. More... »

PAGES

640

Journal

TITLE

Scientific Reports

ISSUE

1

VOLUME

9

Author Affiliations

From Grant

  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-36606-7

    DOI

    http://dx.doi.org/10.1038/s41598-018-36606-7

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30679498


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