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Quercetin potentiates transdifferentiation of bone marrow mesenchymal stem cells into the beta cells in vitro

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Abstract

Purpose

Type 1 diabetes is an autoimmune disease caused by the destruction of β-cells in the pancreas. Bone marrow mesenchymal stem cells are multipotent and easy accessible adult stem cells that may provide options in the treatment of type 1 diabetes. Injured pancreatic extract can promote the differentiation of rat bone marrow mesenchymal stem cells into β-cells. We aimed to observe the effect of quercetin in differentiation and insulin secretion in β-cells.

Methods

Bone marrow mesenchymal stem cells were obtained from the tibiae of rats. Cell surface markers were analyzed by flow cytometry. The cells were treated with rat injured pancreatic extract and quercetin for 2 weeks. Insulin secretion was measured by ELISA. Insulin expression and some islet factors were evaluated by RT-PCR. PDX1, a marker for β-cell function and differentiation, was evaluated by both immunocytochemistry and Western blot. β-cell count was determined by stereology and cell count assay.

Results

ELISA showed significant differences in insulin secretion in the cells treated with RIPE + 20 μM quercetin (0.55 ± 0.01 µg/L) compared with the cells treated with RIPE alone (0.48 ± 0.01 µg/L) (P = 0.026). RT-PCR results confirmed insulin expression in both groups. PDX1 protein was detected in both groups by Western blot and immunocytochemistry. Stereology results showed a significant increase in β-cell number in the RIPE + quercetin-treated cells (47 ± 2.0) when compared with RIPE treatment alone (44 ± 2.5) (P = 0.015).

Conclusions

Quercetin has a strengthening effect on the differentiation of rat bone marrow mesenchymal stem cells into β-cells and increases insulin secretion from the differentiated β-cells in vitro.

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Acknowledgement

This paper has been extracted from the PhD thesis of Behnoosh Miladpour and was supported by Grant Number 93-7228 from Vice-chancellor for Research Affairs of Shiraz University of Medical Sciences.

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Authors and Affiliations

  1. Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

    B. Miladpour, M. Rasti, A. A. Owji, Z. Mostafavipour, Z. Khoshdel & F. Zal

  2. Anatomy Department, Shiraz University of Medical Sciences, Shiraz, Iran

    A. Noorafshan

  3. Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    F. Zal

  4. Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    A. Noorafshan

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  1. B. Miladpour
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  2. M. Rasti
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  3. A. A. Owji
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  5. Z. Khoshdel
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Correspondence to F. Zal.

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Authors do not have conflict of interest in any aspects of specific financial interests and affiliations.

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All animal experiments were approved by the ethics committee of Shiraz University of Medical Sciences.

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Miladpour, B., Rasti, M., Owji, A.A. et al. Quercetin potentiates transdifferentiation of bone marrow mesenchymal stem cells into the beta cells in vitro. J Endocrinol Invest 40, 513–521 (2017). https://doi.org/10.1007/s40618-016-0592-8

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  • DOI: https://doi.org/10.1007/s40618-016-0592-8

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