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

作者：Mehrabi Maryam; Mansouri Kamran; Hosseinkhani Saman; Yarani Reza; Yari Kheirollah; Bakhtiari Mitra; Mostafaie Ali^*

来源：In Vitro Cellular & Developmental Biology-Animal, 2015, 51(6): 595-603.

DOI：10.1007/s11626-015-9866-2

• Diabetes
• Differentiation
• Skin-derived precursors
• Insulin-producing cells

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 beta 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 beta 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.

• 出版日期2015-6