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J Biomol Screen DOI:10.1177/1087057111430253

A human islet cell culture system for high-throughput screening.

Publication TypeJournal Article
Year of Publication2012
AuthorsWalpita, D, Hasaka, T, Spoonamore, J, Vetere, A, Takane, KK, Fomina-Yadlin, D, Fiaschi-Taesch, N, Shamji, A, Clemons, PA, Stewart, AF, Schreiber, SL, Wagner, BK
JournalJ Biomol Screen
Date Published2012 Apr
KeywordsCell Line, Cell Proliferation, Drug Evaluation, Preclinical, Glucose, High-Throughput Screening Assays, Humans, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Primary Cell Culture, Reproducibility of Results, Small Molecule Libraries

A small-molecule inducer of beta-cell proliferation in human islets represents a potential regeneration strategy for treating type 1 diabetes. However, the lack of suitable human beta cell lines makes such a discovery a challenge. Here, we adapted an islet cell culture system to high-throughput screening to identify such small molecules. We prepared microtiter plates containing extracellular matrix from a human bladder carcinoma cell line. Dissociated human islets were seeded onto these plates, cultured for up to 7 days, and assessed for proliferation by simultaneous Ki67 and C-peptide immunofluorescence. Importantly, this environment preserved beta-cell physiological function, as measured by glucose-stimulated insulin secretion. Adenoviral overexpression of cdk-6 and cyclin D(1), known inducers of human beta cell proliferation, was used as a positive control in our assay. This induction was inhibited by cotreatment with rapamycin, an immunosuppressant often used in islet transplantation. We then performed a pilot screen of 1280 compounds, observing some phenotypic effects on cells. This high-throughput human islet cell culture method can be used to assess various aspects of beta-cell biology on a relatively large number of compounds.


Alternate JournalJ Biomol Screen
PubMed ID22156222
Grant ListDP2-DK083048 / DK / NIDDK NIH HHS / United States
U-01 DK0089538 / DK / NIDDK NIH HHS / United States
/ / Howard Hughes Medical Institute / United States