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Diabetologia

Erschienen in:

01.09.2011 | Article

Generation of pancreatic insulin-producing cells from rhesus monkey induced pluripotent stem cells

verfasst von: F. F. Zhu, P. B. Zhang, D. H. Zhang, X. Sui, M. Yin, T. T. Xiang, Y. Shi, M. X. Ding, H. Deng

Erschienen in: Diabetologia | Ausgabe 9/2011

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Abstract

Aims/hypothesis

The generation of induced pluripotent stem cells (iPSCs) provides a promising possibility for type 1 diabetes therapy. However, the generation of insulin-producing cells from iPSCs and evaluation of their efficacy and safety should be achieved in large animals before clinically applying iPSC-derived cells in humans. Here we try to generate insulin-producing cells from rhesus monkey (RM) iPSCs.

Methods

Based on the knowledge of embryonic pancreatic development, we developed a four-stage protocol to generate insulin-producing cells from RM iPSCs. We established a quantitative method using flow cytometry to analyse the differentiation efficiency. In addition, to evaluate the differentiation competence and function of RM iPSC-derived cells, transplantation of stage 3 and 4 cells into immunodeficient mice was performed.

Results

RM iPSCs were sequentially induced to definitive endoderm (DE), pancreatic progenitors (PP), endocrine precursors (EP) and insulin-producing cells. PDX1⁺ PP cells were obtained efficiently from RM iPSCs (over 85% efficiency). The TGF-β inhibitor SB431542 promoted the generation of NGN3⁺ EP cells, which can generate insulin-producing cells in vivo upon transplantation. Finally, after this four-stage differentiation in vitro, insulin-producing cells that could secrete insulin in response to glucose stimulation were obtained. When transplanted into mouse models for diabetes, these insulin-producing cells could decrease blood glucose levels in approximately 50% of the mice.

Conclusions/interpretation

We demonstrate for the first time that RM iPSCs can be differentiated into functional insulin-producing cells, which will provide the basis for investigating the efficacy and safety of autologous iPSC-derived insulin-producing cells in a rhesus monkey model for type 1 diabetes therapy.

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Titel: Generation of pancreatic insulin-producing cells from rhesus monkey induced pluripotent stem cells
verfasst von: F. F. Zhu
P. B. Zhang
D. H. Zhang
X. Sui
M. Yin
T. T. Xiang
Y. Shi
M. X. Ding
H. Deng
Publikationsdatum: 01.09.2011
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 9/2011
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2246-x

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