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Differentiation of multipotent stem cells to insulin-producing cells for treatment of diabetes mellitus: bone marrow- and adipose tissue-derived cells comparison

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Abstract

Background

Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together.

Methods and results

MSCs were pre-induced with nicotinamide, mercaptoethanol, B-27 and b-FGF in L-DMEM for 2 days and re-induced again in supplemented H-DMEM for another 3 days. Expression of five genes in differentiated beta cells was evaluated by Real-time PCR and western blotting and the potency of insulin release in response to glucose stimulation was evaluated by insulin and C-peptide ELISA kit. The differentiated cells were evaluated by immunocytochemistry staining for Insulin and PDX-1. Quantitative RT-PCR results showed up-regulation of four genes in differentiated beta-islet cells (Insulin, Ngn-3, Pax-4 and Pdx-1) compared with the control. Western blot analysis showed that MSCs cells mainly produced proinsulin and insulin after differentiation but nestin was more expressed in pre-differentiated stem cells. Glucose and insulin secretion assay showed that insulin levels and C-peptide secretion were significantly increased in response to 10 mM glucose.

Conclusions

Our study showed that both adipose and bone marrow stem cells could differentiate into functional beta-islet cells but it seems that adipose stem cells could be a better choice for treatment of diabetes mellitus according to their higher potency.

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Acknowledgements

This work was supported by the Research Committee of Zabol University of Medical Sciences, Zabol, Iran. We would like to give special thanks to Medical Biotechnology Center of CinnaGen Co. for their support to publish this article.

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Authors and Affiliations

  1. Department of Pediatric Endocrinology and Metabolism, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zahra Eydian

  2. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran

    Alaleh Mohammad Ghasemi, Maryam Khosravi, Sima Momtaz, Sanaz Riki, Laleh Rafighdoost & Reza Entezari Heravi

  3. CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran

    Samira Ansari, Ali Naghi Kamali & Reza Entezari Heravi

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  1. Zahra Eydian
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Correspondence to Reza Entezari Heravi.

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Eydian, Z., Mohammad Ghasemi, A., Ansari, S. et al. Differentiation of multipotent stem cells to insulin-producing cells for treatment of diabetes mellitus: bone marrow- and adipose tissue-derived cells comparison. Mol Biol Rep 49, 3539–3548 (2022). https://doi.org/10.1007/s11033-022-07194-7

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  • DOI: https://doi.org/10.1007/s11033-022-07194-7

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