Generation of insulin-producing β-like cells from human iPS cells in a defined and completely xeno-free culture system

Human induced pluripotent stem （hiPS） cells are considered a potential source for the generation of insulin-producing pancreatic β-ceUs because of their differentiation capacity. In this study, we have developed a five-step xeno-free culture system to efficiently dif- ferentiate hiPS cells into insu...

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Published inJournal of molecular cell biology Vol. 6; no. 5; pp. 394 - 408
Main Authors Shahjalal, Hussain Md, Shiraki, Nobuaki, Sakano, Daisuke, Kikawa, Kazuhide, Ogaki, Soichiro, Baba, Hideo, Kume, Kazuhiko, Kume, Shoen
Format Journal Article
LanguageEnglish
Published United States 01.10.2014
Subjects
Cell Culture Techniques
Cell Differentiation
Cell Line
Culture Media
HIPS
Humans
Induced Pluripotent Stem Cells - cytology
Insulin - biosynthesis
Insulin-Secreting Cells - cytology
iPS
NOGGIN
分化能力
培养系统
异物
细胞分化
胰岛素分泌
xeno-free differentiation
β-cells
diabetes
hiPS cells
cell therapy
pancreas
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Summary:Human induced pluripotent stem （hiPS） cells are considered a potential source for the generation of insulin-producing pancreatic β-ceUs because of their differentiation capacity. In this study, we have developed a five-step xeno-free culture system to efficiently dif- ferentiate hiPS cells into insulin-producing cells in vitro. We found that a high NOGGIN concentration is crucial for specifically inducing the differentiation first into pancreatic and duodenal homeobox-1 （PDX1）-positive pancreatic progenitors and then into neurogenin 3 （NGN3）-expressing pancreatic endocrine progenitors, while suppressing the differentiation into hepatic or intestinal cells. We also found that a combination of 3-isobutyl-l-methylxanthine （IBMX）, exendin-4, and nicotinamide was important for the differentiation into insulin single-positive cells that expressed various pancreatic β-cell markers. Most notably, the differentiated cells contained en- dogenous C-peptide pools that were released in response to various insulin secretagogues and high levels of glucose. Therefore, our results demonstrate the feasibility of generating hiPS-derived pancreatic β-ceUs under xeno-free conditions and highlight their poten- tial to treat patients with type I diabetes.
Bibliography:31-2002/Q
diabetes, pancreas, ceil therapy, hiPS ceils, xeno-free differentiation, β-cells
Human induced pluripotent stem （hiPS） cells are considered a potential source for the generation of insulin-producing pancreatic β-ceUs because of their differentiation capacity. In this study, we have developed a five-step xeno-free culture system to efficiently dif- ferentiate hiPS cells into insulin-producing cells in vitro. We found that a high NOGGIN concentration is crucial for specifically inducing the differentiation first into pancreatic and duodenal homeobox-1 （PDX1）-positive pancreatic progenitors and then into neurogenin 3 （NGN3）-expressing pancreatic endocrine progenitors, while suppressing the differentiation into hepatic or intestinal cells. We also found that a combination of 3-isobutyl-l-methylxanthine （IBMX）, exendin-4, and nicotinamide was important for the differentiation into insulin single-positive cells that expressed various pancreatic β-cell markers. Most notably, the differentiated cells contained en- dogenous C-peptide pools that were released in response to various insulin secretagogues and high levels of glucose. Therefore, our results demonstrate the feasibility of generating hiPS-derived pancreatic β-ceUs under xeno-free conditions and highlight their poten- tial to treat patients with type I diabetes.
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ISSN:1674-2788
1759-4685
DOI:10.1093/jmcb/mju029