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In vitro proliferation of adult human beta-cells

Sauter, Nadine S
Prazak, Richard
Donath, Marc Y
Published in PLOS ONE. 2012, vol. 7, no. 4, p. e35801
Abstract A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1) analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells") population were plated on extracellular matrix from rat (804G) and human bladder carcinoma cells (HTB9) or bovine corneal endothelial ECM (BCEC). Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted) or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted), independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05).These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.
Keywords AdultAgedAnimalsCattleCell ProliferationCellsCulturedExtracellular Matrix/chemistry/metabolismGlucagon-Like Peptide 1/metabolismHumansInsulin-Secreting Cells/cytology/metabolismMiddle AgedRatsTissue DonorsYoung Adult
PMID: 22563404
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Research group Fonction de l'îlot de Langerhans (324)
Project Novo Nordisk
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RUTTI ROCH, Sabine et al. In vitro proliferation of adult human beta-cells. In: PLOS ONE, 2012, vol. 7, n° 4, p. e35801. doi: 10.1371/journal.pone.0035801 https://archive-ouverte.unige.ch/unige:26211

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Deposited on : 2013-02-05

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