PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells
<h3>Aim</h3><p dir="ltr">Beta cell replacement strategies are a promising alternative for diabetes treatment. Human pluripotent stem cells (hPSCs) serve as a scalable source for producing insulin-secreting cells for transplantation therapy. We recently generated novel hPS...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , |
| منشور في: |
2020
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| الموضوعات: | |
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إضافة وسم
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| الملخص: | <h3>Aim</h3><p dir="ltr">Beta cell replacement strategies are a promising alternative for diabetes treatment. Human pluripotent stem cells (hPSCs) serve as a scalable source for producing insulin-secreting cells for transplantation therapy. We recently generated novel hPSC-derived pancreatic progenitors, expressing high levels of the transcription factor NKX6.1, in the absence of PDX1 (PDX1<sup>−</sup>/NKX6.1<sup>+</sup>). Herein, our aim was to characterize this novel population and assess its ability to differentiate into insulin-secreting beta cells in vitro.</p><h3>Materials and Methods</h3><p dir="ltr">Three different hPSC lines were differentiated into PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors, which were further differentiated into insulin-secreting cells using two different protocols. The progenitors and beta cells were extensively characterized. Transcriptome analysis was performed at different stages and compared with the profiles of various pancreatic counterparts.</p><h3>Results</h3><p dir="ltr">PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors expressed high levels of nestin, a key marker of pancreatic islet-derived progenitors, in the absence of E-cadherin, similar to pancreatic mesenchymal stem cells. At progenitor stage, comparison of the two populations showed downregulation of pancreatic epithelial genes and upregulation of neuronal development genes in PDX1<sup>−</sup>/NKX6.1<sup>+</sup> cells in comparison to the PDX1<sup>+</sup>/NKX6.1<sup>+</sup> cells. Interestingly, on further differentiation, PDX1<sup>−</sup>/NKX6.1<sup>+</sup> cells generated mono-hormonal insulin<sup>+</sup> cells and activated pancreatic key genes, such as PDX1. The transcriptome profile of PDX1<sup>−</sup>/NKX6.1<sup>+</sup>-derived beta (3D-beta) was closely similar to those of human pancreatic islets and purified hPSC-derived beta cells. Also, the 3D-beta cells secreted C-peptide in response to increased glucose concentrations indicating their functionality.</p><h3>Conclusion</h3><p dir="ltr">These findings provide a novel source of insulin-secreting cells that can be used for beta cell therapy for diabetes.</p><h2>Other Information</h2><p dir="ltr">Published in: Diabetes/Metabolism Research and Reviews<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1002/dmrr.3400" target="_blank">http://dx.doi.org/10.1002/dmrr.3400</a></p> |
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