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Exploring the effec...
Exploring the effect of epigenetic modifiers on developing insulin-secreting cells
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- Elsharkawi, Ibrahim (author)
- Univ Sharjah, U Arab Emirates
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- Parambath, Divyasree (author)
- Univ Sharjah, U Arab Emirates
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- Saber-Ayad, Maha (author)
- Univ Sharjah, U Arab Emirates; Cairo Univ, Egypt
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- Khan, Amir Ali (author)
- Univ Sharjah, U Arab Emirates
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- El-Serafi, Ahmed Taher, 1977- (author)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Hand- och plastikkirurgiska kliniken US,Univ Sharjah, U Arab Emirates; Suez Canal Univ, Egypt
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(creator_code:org_t)
- 2019-11-21
- 2020
- English.
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In: HUMAN CELL. - : SPRINGER JAPAN KK. - 1749-0774 .- 0914-7470. ; 33, s. 1-9
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Stem cells; Beta cells; Diabetes; Differentiation; epigenetic modifiers
Publication and Content Type
- ref (subject category)
- art (subject category)
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