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Controlled aggregation of primary human pancreatic islet cells leads to glucose-responsive pseudoislets comparable to native islets.

Hilderink J, Spijker S, Carlotti F, Lange L, Engelse M, van Blitterswijk C, de Koning E, Karperien M, van Apeldoorn A - J. Cell. Mol. Med. (2015)

Bottom Line: To reduce diffusion restrictions and improve islet cell survival, the generation of islets with optimal dimensions by dispersion followed by reassembly of islet cells, can help limit the length of diffusion pathways.The re-associated human islet cells showed an a-typical core shell configuration with beta cells predominantly on the outside unlike human islets, which became more randomized after implantation similar to native human islets.The agarose microwell platform was shown to be an easy and very reproducible method to aggregate pancreatic islet cells with high accuracy providing a reliable tool to study cell-cell interactions between insuloma and/or primary islet cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Developmental Bioengineering, University of Twente, Enschede, The Netherlands.

No MeSH data available.


Related in: MedlinePlus

Human islet cell aggregates are viable and function in vivo. (A) 14 days after transplantation under the kidney capsule of immunodeficient mice, human islet cell aggregates (1000 cells/aggregate) show a heterogenous cell architecture that is similar to intact human islets, with alpha- and beta cells randomly spread throughout the aggregate; scale bar = 50 μm. (B) Serum C-peptide levels seem higher in transplanted mice compared to control mice at day 7 and 14 after transplantation (n = 3–5 mice, 2 donors); error bars represent mean ± SD.
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fig06: Human islet cell aggregates are viable and function in vivo. (A) 14 days after transplantation under the kidney capsule of immunodeficient mice, human islet cell aggregates (1000 cells/aggregate) show a heterogenous cell architecture that is similar to intact human islets, with alpha- and beta cells randomly spread throughout the aggregate; scale bar = 50 μm. (B) Serum C-peptide levels seem higher in transplanted mice compared to control mice at day 7 and 14 after transplantation (n = 3–5 mice, 2 donors); error bars represent mean ± SD.

Mentions: Following 2 days of in vitro aggregation in microwells primary human islet cell aggregates were transplanted for 14 days under the kidney capsule of NOD/SCID mice. Figure6A shows that after 14 days in vivo, human islet cell aggregates exhibit a normal cellular architecture. Quantification of TUNEL+ cells showed negligible, 0.95 ± 0.75%, apoptotic cell death. Human C-peptide, around 200 pmol/l (average of 2 human donors) at day 7 and 14, was observed in serum of transplanted mice whereas the human C-peptide concentrations in non-transplanted mice were undetectable at day 7 and 14 post transplantation (Fig.6B).


Controlled aggregation of primary human pancreatic islet cells leads to glucose-responsive pseudoislets comparable to native islets.

Hilderink J, Spijker S, Carlotti F, Lange L, Engelse M, van Blitterswijk C, de Koning E, Karperien M, van Apeldoorn A - J. Cell. Mol. Med. (2015)

Human islet cell aggregates are viable and function in vivo. (A) 14 days after transplantation under the kidney capsule of immunodeficient mice, human islet cell aggregates (1000 cells/aggregate) show a heterogenous cell architecture that is similar to intact human islets, with alpha- and beta cells randomly spread throughout the aggregate; scale bar = 50 μm. (B) Serum C-peptide levels seem higher in transplanted mice compared to control mice at day 7 and 14 after transplantation (n = 3–5 mice, 2 donors); error bars represent mean ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549034&req=5

fig06: Human islet cell aggregates are viable and function in vivo. (A) 14 days after transplantation under the kidney capsule of immunodeficient mice, human islet cell aggregates (1000 cells/aggregate) show a heterogenous cell architecture that is similar to intact human islets, with alpha- and beta cells randomly spread throughout the aggregate; scale bar = 50 μm. (B) Serum C-peptide levels seem higher in transplanted mice compared to control mice at day 7 and 14 after transplantation (n = 3–5 mice, 2 donors); error bars represent mean ± SD.
Mentions: Following 2 days of in vitro aggregation in microwells primary human islet cell aggregates were transplanted for 14 days under the kidney capsule of NOD/SCID mice. Figure6A shows that after 14 days in vivo, human islet cell aggregates exhibit a normal cellular architecture. Quantification of TUNEL+ cells showed negligible, 0.95 ± 0.75%, apoptotic cell death. Human C-peptide, around 200 pmol/l (average of 2 human donors) at day 7 and 14, was observed in serum of transplanted mice whereas the human C-peptide concentrations in non-transplanted mice were undetectable at day 7 and 14 post transplantation (Fig.6B).

Bottom Line: To reduce diffusion restrictions and improve islet cell survival, the generation of islets with optimal dimensions by dispersion followed by reassembly of islet cells, can help limit the length of diffusion pathways.The re-associated human islet cells showed an a-typical core shell configuration with beta cells predominantly on the outside unlike human islets, which became more randomized after implantation similar to native human islets.The agarose microwell platform was shown to be an easy and very reproducible method to aggregate pancreatic islet cells with high accuracy providing a reliable tool to study cell-cell interactions between insuloma and/or primary islet cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Developmental Bioengineering, University of Twente, Enschede, The Netherlands.

No MeSH data available.


Related in: MedlinePlus