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Differentiation of human skin-derived precursor cells into functional islet-like insulin-producing cell clusters

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Abstract

Advances in cell-replacement strategies for diabetes have focused on renewable sources of glucose-responsive, insulin-producing cells (IPCs). One of the most proper alternatives is multipotent skin-derived precursors cells (SKPs), which can be differentiated into IPCs. In this study, we reported the isolation and expansion of human skin-derived precursors (hSKPs) followed by their differentiation into IPCs in vitro, through exposure to suitable differentiation factors. The gene expression of endocrine β cell markers was analyzed by reverse transcriptase-polymerase chain reaction. In addition, insulin production was examined immunocytochemically, and insulin and C-peptide secretion were examined using enzyme-linked immunosorbent assay. Dithizone-stained cellular clusters were observed after approximately 20 d. The clusters were found to be immunoreactive to insulin and expressed multiple genes related to pancreatic β cell development and function: insulin, Pdx-1, Islet-1, NeuroD, Glut-2, Pax-4, Ngn-3, and Nkx2.2, but not to other pancreas-specific hormones such as glucagon and somatostatin. Cellular clusters were also able to secrete detectable amounts of insulin and C-peptide in a glucose dose-dependent manner. These findings suggest that human SKPs can differentiate into functional IPCs. This may offer a safer cell source for future stem cell-based therapies.

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Acknowledgments

The present work was financially supported by the Iranian Council of Stem Cell Technology and Deputy University for Research of Kermanshah Medical University—Ministry of Health and Medical education. We thank our colleagues (Kermanshah Medical Biology Research Center, Kermanshah University of Medical Sciences) for their valuable assistance.

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Authors and Affiliations

  1. Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran

    Maryam Mehrabi

  2. Medical Biology Research Center, Kermanshah University of Medical Sciences, P.O. Box 6714869914, Sorkheh lizheh, Kermanshah, Iran

    Maryam Mehrabi, Kamran Mansouri, Reza Yarani, Kheirollah Yari, Mitra Bakhtiari & Ali Mostafaie

  3. Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Saman Hosseinkhani

  4. Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Ali Mostafaie

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  1. Maryam Mehrabi
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  2. Kamran Mansouri
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  3. Saman Hosseinkhani
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  4. Reza Yarani
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  6. Mitra Bakhtiari
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  7. Ali Mostafaie
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Correspondence to Ali Mostafaie.

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Editor: T. Okamoto

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Mehrabi, M., Mansouri, K., Hosseinkhani, S. et al. Differentiation of human skin-derived precursor cells into functional islet-like insulin-producing cell clusters. In Vitro Cell.Dev.Biol.-Animal 51, 595–603 (2015). https://doi.org/10.1007/s11626-015-9866-2

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  • DOI: https://doi.org/10.1007/s11626-015-9866-2

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