Dr. Hussain Md. Shahjalal Assistant Professor, Department of Biochemistry & Molecular Biology

Research Interest

Stem Cell Biology

Others

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


Shahjalal HM1, Shiraki N2, Sakano D1, Kikawa K3, Ogaki S2, Baba H4, Kume K5, Kume S6.


Abstract



Human induced pluripotent stem (hiPS) cells are considered a potential source for the generation of insulin-producing pancreatic β-cells because of their differentiation capacity. In this study, we have developed a five-step xeno-free culture system to efficiently differentiate 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-1-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 endogenous 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-cells under xeno-free conditions and highlight their potential to treat patients with type 1 diabetes.


© The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.





KEYWORDS:


cell therapy; diabetes; hiPS cells; pancreas; xeno-free differentiation; β-cells






PMID:

24970864

[PubMed - in process]