Differentiation of Human-Induced Pluripotent Stem Cell-Derived Endocrine Progenitors to Islet-like Cells Using a Dialysis Suspension Culture System

The production of functional islet-like cells from human-induced pluripotent stem cells (hiPSCs) is a promising strategy for the therapeutic use and disease modeling for type 1 diabetes. However, the production cost of islet-like cells is extremely high due to the use of expensive growth factors for...

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Main Authors: Hyunjin Choi, Marie Shinohara, Masato Ibuki, Masaki Nishikawa, Yasuyuki Sakai
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/8/2017
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spelling doaj-c05a68af74544e2fb6acc0ae036ada612021-08-26T13:37:24ZengMDPI AGCells2073-44092021-08-01102017201710.3390/cells10082017Differentiation of Human-Induced Pluripotent Stem Cell-Derived Endocrine Progenitors to Islet-like Cells Using a Dialysis Suspension Culture SystemHyunjin Choi0Marie Shinohara1Masato Ibuki2Masaki Nishikawa3Yasuyuki Sakai4Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8654, JapanInstitute of Industrial Science, The University of Tokyo, Tokyo 153-8505, JapanInstitute of Industrial Science, The University of Tokyo, Tokyo 153-8505, JapanDepartment of Chemical System Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8654, JapanDepartment of Chemical System Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8654, JapanThe production of functional islet-like cells from human-induced pluripotent stem cells (hiPSCs) is a promising strategy for the therapeutic use and disease modeling for type 1 diabetes. However, the production cost of islet-like cells is extremely high due to the use of expensive growth factors for differentiation. In a conventional culture method, growth factors and beneficial autocrine factors remaining in the culture medium are removed along with toxic metabolites during the medium change, and it limits the efficient utilization of those factors. In this study, we demonstrated that the dialysis suspension culture system is possible to reduce the usage of growth factors to one-third in the differentiation of hiPSC-derived endocrine progenitor cells to islet-like cells by reducing the medium change frequency with the refinement of the culture medium. Furthermore, the expression levels of hormone-secretion-related genes and the efficiency of differentiation were improved with the dialysis suspension culture system, possibly due to the retaining of autocrine factors. In addition, we confirmed several improvements required for the further study of the dialysis culture system. These findings showed the promising possibility of the dialysis suspension culture system for the low-cost production of islet-like cells.https://www.mdpi.com/2073-4409/10/8/2017pancreatic β cellislet-like cellhiPSCdifferentiationdialysissuspension culture
collection DOAJ
language English
format Article
sources DOAJ
author Hyunjin Choi
Marie Shinohara
Masato Ibuki
Masaki Nishikawa
Yasuyuki Sakai
spellingShingle Hyunjin Choi
Marie Shinohara
Masato Ibuki
Masaki Nishikawa
Yasuyuki Sakai
Differentiation of Human-Induced Pluripotent Stem Cell-Derived Endocrine Progenitors to Islet-like Cells Using a Dialysis Suspension Culture System
Cells
pancreatic β cell
islet-like cell
hiPSC
differentiation
dialysis
suspension culture
author_facet Hyunjin Choi
Marie Shinohara
Masato Ibuki
Masaki Nishikawa
Yasuyuki Sakai
author_sort Hyunjin Choi
title Differentiation of Human-Induced Pluripotent Stem Cell-Derived Endocrine Progenitors to Islet-like Cells Using a Dialysis Suspension Culture System
title_short Differentiation of Human-Induced Pluripotent Stem Cell-Derived Endocrine Progenitors to Islet-like Cells Using a Dialysis Suspension Culture System
title_full Differentiation of Human-Induced Pluripotent Stem Cell-Derived Endocrine Progenitors to Islet-like Cells Using a Dialysis Suspension Culture System
title_fullStr Differentiation of Human-Induced Pluripotent Stem Cell-Derived Endocrine Progenitors to Islet-like Cells Using a Dialysis Suspension Culture System
title_full_unstemmed Differentiation of Human-Induced Pluripotent Stem Cell-Derived Endocrine Progenitors to Islet-like Cells Using a Dialysis Suspension Culture System
title_sort differentiation of human-induced pluripotent stem cell-derived endocrine progenitors to islet-like cells using a dialysis suspension culture system
publisher MDPI AG
series Cells
issn 2073-4409
publishDate 2021-08-01
description The production of functional islet-like cells from human-induced pluripotent stem cells (hiPSCs) is a promising strategy for the therapeutic use and disease modeling for type 1 diabetes. However, the production cost of islet-like cells is extremely high due to the use of expensive growth factors for differentiation. In a conventional culture method, growth factors and beneficial autocrine factors remaining in the culture medium are removed along with toxic metabolites during the medium change, and it limits the efficient utilization of those factors. In this study, we demonstrated that the dialysis suspension culture system is possible to reduce the usage of growth factors to one-third in the differentiation of hiPSC-derived endocrine progenitor cells to islet-like cells by reducing the medium change frequency with the refinement of the culture medium. Furthermore, the expression levels of hormone-secretion-related genes and the efficiency of differentiation were improved with the dialysis suspension culture system, possibly due to the retaining of autocrine factors. In addition, we confirmed several improvements required for the further study of the dialysis culture system. These findings showed the promising possibility of the dialysis suspension culture system for the low-cost production of islet-like cells.
topic pancreatic β cell
islet-like cell
hiPSC
differentiation
dialysis
suspension culture
url https://www.mdpi.com/2073-4409/10/8/2017
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