Chemically defined conditions for long-term maintenance of pancreatic progenitors derived from human induced pluripotent stem cells
Open accessAbstract
Large numbers of hormone-releasing cells, approximately 10 9 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 10 4-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.
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Several studies have demonstrated the ability to propagate the pancreatic progenitor population generated during the middle portion of the differentiation protocol.
“Several studies, however, have demonstrated the ability to propagate the pancreatic progenitor population that is generated during the middle portion of the differentiation protocol.181,182”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [182]
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- Authors
- Konagaya, S., & Iwata, H.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Iwata, Hiroo
- ORCID
- Iwata, Hiroo
- Venue
- Scientific Reports
- Published
- 2019-01-24
- Volume
- 9
- Issue
- 1
- Pages
- 640-640
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6345937
- OpenAlex
- W2914023179
- Cited by
- 30
- References
- 26
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 8 · 2022: 2 · 2021: 8 · 2020: 1 · 2019: 2
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- MEXT | Japan Society for the Promotion of Science (16K21116, Center of Innovation (COI) Program)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- pancreatic progenitors, human induced pluripotent stem cells, chemically defined medium, 3D cell culture, PDX1, beta-like cells, endocrine differentiation, cell expansion, cryopreservation, RSPO1, CHIR99021, fibroblast growth factor 7, SB431542, epidermal growth factor
- MeSH terms
- Benzamides, Cell Differentiation, Dioxoles, Epidermal Growth Factor, Humans, Pancreas, Pyridines, Pyrimidines, Cell Proliferation, Insulin-Secreting Cells, Endocrine Cells, Induced Pluripotent Stem Cells
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