Investigating the role of the histone deacetylases-inhibitor suberanilohydroxamic acid in the differentiation of stem cells into insulin secreting cells

• Introduction: The United Arab Emirates has the second incidence of diabetes in the world. The current diabetes management plans are associated with many complications and do not provide a cure. Stem cells offer hope for permanent alleviation of this health problem through the possible differentiation into insulin-secreting cells. The current methods for the differentiation do not produce homogeneous beta-cell populations. Histone deacetylation is an epigenetic silencing mechanism that can render many genes irresponsive to the induction protocols. This study aimed at investigating the effect of the histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) on the production of functional beta cells, based on a mesenchymal stem cells model. Methods: MG63 cells were treated for three consecutive days with SAHA, followed by a three-steps of beta cells differentiation protocol, with media-contained retinoic acid, epidermal growth factor, nicotinamide and exendin-4 at different stages. Then, glucose-stimulated insulin secretion was conducted to assess the functional state of the differentiated cells.Results: Pretreating the cells with SAHA enhanced the insulin production and secretion in comparison to the control (PBS) and the vehicle dimethyl sulfoxide, as shown by the immunofluorescence detection of insulin and the transcription factor “PDX1”, as well as an increase in insulin secretion in the media. Gene expression analysis showed that SAHA pretreated cells had more induction of the studied markers when challenged with high glucose level.Conclusion: Such findings indicate a novel approach to enhance the ability of stem cells to differentiate into insulin-producing cells with potential therapeutic implications.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Diabetes; epigenetics; histone acetylation; insulin; stem cells

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