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Diabetologia

Erschienen in:

01.10.2005 | Article

Insulin-producing cells derived from human pancreatic non-endocrine cell cultures reverse streptozotocin-induced hyperglycaemia in mice

verfasst von: M. Zhao, S. A. Amiel, M. R. Christie, M. Rela, N. Heaton, G. C. Huang

Erschienen in: Diabetologia | Ausgabe 10/2005

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Abstract

Aims/hypothesis

The aim of the study was to investigate the potential of human pancreatic non-endocrine cells to transdifferentiate into endocrine cells that would be capable of secreting insulin in response to glucose and ameliorating insulin-deficient diabetes after transplantation.

Materials and methods

Cell fractions enriched with exocrine cells after human islet isolation were treated with streptozotocin to remove residual beta cells, grown in monolayer culture to allow de-differentiation, transferred to cluster culture for redifferentiation in the presence of activin A, betacellulin, nicotinamide and glucose, supplemented with 10% FCS, and administered to streptozotocin-induced diabetic SCID mice. A subset of cells was transfected with the IPF1 gene (also known as PDX1) before transdifferentiation.

Results

No insulin was detectable in cell preparations after 5 days of treatment with streptozotocin. In monolayer culture, 90% of the streptozotocin-treated pancreatic cells co-expressed cytokeratin-19 and vimentin at 2 weeks and 60% expressed nestin at 4 weeks. Cell cultures with a high proportion of nestin-expressing cells had greater plasticity for transdifferentiation into cells with phenotypic and functional markers of beta cells, this property being significantly enhanced by transfection with IPF1 gene and leading to 15±6.7% insulin-positive cells after transplantation vs. 0.01% of cells transplanted after streptozotocin treatment alone. These cells improved glucose control in all of 42 diabetic mice after transplantation, restoring normoglycaemia in 40%.

Conclusions/interpretation

Human pancreatic cells are a potential source of new glucose-responsive insulin-producing cells that may be developed further for clinical use.

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Titel: Insulin-producing cells derived from human pancreatic non-endocrine cell cultures reverse streptozotocin-induced hyperglycaemia in mice
verfasst von: M. Zhao
S. A. Amiel
M. R. Christie
M. Rela
N. Heaton
G. C. Huang
Publikationsdatum: 01.10.2005
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 10/2005
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-005-1888-y

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Abstract

Aims/hypothesis

Materials and methods

Results

Conclusions/interpretation

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Reply to comment on: Biason-Lauber A, Boehm B, Lang-Muritano M et al. (2005) Association of childhood type 1 diabetes mellitus with a variant of PAX4: possible link to beta cell regenerative capacity. Diabetologia 48:900–905