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Exploring the effect of epigenetic modifiers on developing insulin-secreting cells
Univ Sharjah, U Arab Emirates.
Univ Sharjah, U Arab Emirates.
Univ Sharjah, U Arab Emirates; Cairo Univ, Egypt.
Univ Sharjah, U Arab Emirates.
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2020 (English)In: HUMAN CELL, ISSN 1749-0774, Vol. 33, p. 1-9Article in journal (Refereed) Published
Abstract [en]

Diabetes is a worldwide health problem with increasing incidence. The current management modalities did not succeed to decrease comorbidities. This study aimed at enhancing the regenerative solution for diabetes by improving the differentiation of mesenchymal stromal cells (MSC) into glucose-sensitive, insulin-secreting cells through an epigenetic modification approach. A 3-day treatment protocol with the epigenetic modifiers, either decitabine (5-aza-2 -deoxycytidine; Aza); a DNA methylation inhibitor or Vorinostat (suberoylanilide hydroxamic acid; SAHA); a histone deacetylase inhibitor was added to two different human stem cell lines. The cells followed a multi-step differentiation protocol that provided the critical triggers in a temporal approach. Aza-pretreated group showed higher intracellular expression of insulin and the transcription factor PDX-1. The cells responded to the high glucose challenge by secreting insulin in the media, as shown by ELISA. Gene expression showed induction of the genes for insulin, the glucose transporter 2, glucokinase, as well as the transcription factors MafA and NKX6.1. Although SAHA showed upregulation of insulin secretion, in comparison to control, the cells could not respond to the high glucose challenge. Interestingly, Aza-treated cells showed a significant decrease in the global DNA methylation level at the end of the culture. In conclusion, this additional step with Aza could enhance the response of MSC to the classical differentiation protocol for insulin-secreting cells and may help in establishing a regenerative solution for patients with diabetes.

Place, publisher, year, edition, pages
SPRINGER JAPAN KK , 2020. Vol. 33, p. 1-9
Keywords [en]
Stem cells; Beta cells; Diabetes; Differentiation; epigenetic modifiers
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-162505DOI: 10.1007/s13577-019-00292-yISI: 000497841200001PubMedID: 31755075OAI: oai:DiVA.org:liu-162505DiVA, id: diva2:1379008
Note

Funding Agencies|Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences [MRG-6112013-2014]; University of Sharjah, UAE

Available from: 2019-12-16 Created: 2019-12-16 Last updated: 2024-05-16

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El-Serafi, Ahmed Taher

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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Hand and Plastic Surgery
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