Department of Bio-anylatical Sciences, Guru Nanak Khalsa College of Arts, Science & Commerce, Nathalal Parekh Marg, Matunga East, Mumbai 400019, Maharashtra, India; Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College & Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra 411018, India.
School of Regenerative Medicine, Manipal University, MAHE, GKVK Post, Bellary Road Allalasandra, Near Royal Orchid Yelahanka, Bangalore 560065, India.
Life Sci. 2019 Jan 1;216:287-294. doi: 10.1016/j.lfs.2018.11.028. Epub 2018 Nov 13.
To induce differentiation of human amniotic membrane derived mesenchymal stem cells (hAMMSCs) into insulin producing cells (IPCs) by treating with somatocrinin or growth hormone releasing hormone (GHRH) and Insulin-like growth factor-1 (IGF-1).
In this investigation, we cultivated and characterized hAMMSCs and then treated with IGF-1 and somatocrinin to find out whether this combination gives better yield of insulin producing cells. We showed that hAMMSCs can give rise to IPCs on exposure to serum-free defined media containing specific growth factors and differentiating agents in presence of IGF-1 and somatocrinin.
A combination of IGF-1 and somatocrinin lead to differentiation of large number of IPCs from hAMMSCs. These IPCs were found to be positive for dithizone indicating their insulin secretory mechanism. Moreover these cells were also found to be positive for C-peptide. IPCs released insulin in response to glucose challenge. Gene expression analysis exhibited significant up-regulation of pancreatic transcription factor GLUT2 and Insulin.
Our data thus demonstrates for the first time that somatocrinin and IGF-1 synergistically enhance the differentiation of hAMMSCs into IPCs.
通过用生长激素释放激素(GHRH)和胰岛素样生长因子-1(IGF-1)处理,将人羊膜间充质干细胞(hAMMSCs)诱导分化为胰岛素产生细胞(IPCs)。
在这项研究中,我们培养和鉴定了 hAMMSCs,然后用 IGF-1 和促生长激素释放激素处理,以确定这种组合是否能产生更多的胰岛素产生细胞。我们表明,hAMMSCs 在含有特定生长因子和分化剂的无血清定义培养基中暴露于 IGF-1 和促生长激素释放激素时,可以产生 IPCs。
IGF-1 和促生长激素释放激素的组合导致大量的 IPCs 从 hAMMSCs 中分化出来。这些 IPCs 对二硫腙呈阳性,表明它们具有胰岛素分泌机制。此外,这些细胞也对 C 肽呈阳性。IPC 在受到葡萄糖刺激时会释放胰岛素。基因表达分析显示,胰腺转录因子 GLUT2 和胰岛素的表达显著上调。
我们的数据首次表明,促生长激素释放激素和 IGF-1 协同增强了 hAMMSCs 向 IPCs 的分化。