Proliferation of sorted human and rat beta cells
Open accessAbstract
Aims/hypothesis The aim of the study was to determine whether purified beta cells can replicate in vitro and whether this is enhanced by extracellular matrix (ECM) and growth factors.Methods Human beta cells were purified by FACS by virtue of their high zinc content using Newport Green, and excluding ductal and dead cells. Rat beta cells were sorted by autofluorescence or using the same method developed for human cells. Cells were plated on poly-L-lysine or ECMs from rat or human bladder carcinoma cells or bovine corneal ECM and incubated in the presence of BrdU with or without growth factors.Results The newly developed method for sorting human beta cells yields a population containing 91.4 +/- 2.8% insulin-positive cells with a low level of spontaneous apoptosis and a robust secretory response to glucose. Beta cells from 8-week-old rats proliferated in culture and this was increased by ECM. Among growth factors, only human growth hormone (hGH) and the glucagon-like peptide-1 analogue liraglutide enhanced proliferation of rat beta cells, with a significant increase on both poly-L-lysine and ECM. By contrast, sorted adult human beta cells from 16 donors aged 48.9 +/- 14.3 years (range 16-64 years) failed to replicate demonstrably in vitro regardless of the substratum or growth factors used.Conclusions/interpretation These findings indicate that, in our conditions, the fully differentiated human adult insulin-producing beta cell was unable to proliferate in vitro. This has important implications for any attempt to expand cells from pancreases of donors of this age group. By contrast, the rat beta cells used here were able to divide in vitro, and this was enhanced by ECM, hGH and liraglutide.
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Induction of human islet β-cell proliferation remains an unattained goal, with studies reporting inconsistent mitogenic responses.
“Likewise, induction of human islet β-cell proliferation remains an unattained goal, with studies reporting inconsistent mitogenic responses5,6.”
From PDGF signalling controls age-dependent proliferation in pancreatic β-cells (2011) · cites this paper as [6]
Age-dependent signalling competence might explain earlier findings of inconsistent human β-cell responses to other mitogens.
“Such age-dependent signalling competence might explain earlier findings of inconsistent human β-cell responses to other mitogens5,6.”
From PDGF signalling controls age-dependent proliferation in pancreatic β-cells (2011) · cites this paper as [6]
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- Authors
- Parnaud, G., Bosco, D., Berney, T., Pattou, F., Kerr-Conte, J., Donath, M. Y., Bruun, C., Mandrup-Poulsen, T., Billestrup, N., & Halban, P. A.
- Affiliations
- University of Geneva (CH)
- University Hospital of Geneva (CH)
- Inserm (FR)
- Karolinska Institutet (SE)
- Corresponding author
- Parnaud, G.
- Venue
- Diabetologia
- Published
- 2007-11-10
- Volume
- 51
- Issue
- 1
- Pages
- 91-100
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W1988702698
- Cited by
- 232
- References
- 46
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 12 · 2020: 8 · 2019: 5 · 2018: 7 · 2017: 14 · 2016: 14 · 2015: 15 · 2014: 21 · 2013: 25 · 2012: 20
- FWCI
- 19.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, other-oa)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Novo Nordisk
- Université de Genève
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- beta-cell proliferation, extracellular matrix, growth factors, liraglutide, human growth hormone, beta-cell expansion, donor age
- MeSH terms
- Adolescent, Adult, Animals, Cell Differentiation, Cell Separation, Diabetes Mellitus, Extracellular Matrix, Flow Cytometry, Humans, Middle Aged, Species Specificity, Islets of Langerhans Transplantation, Cell Culture Techniques, Insulin-Secreting Cells, Rats
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