Neuronal Restrictive Silencing Factor Silencing Induces Human Amniotic Fluid-Derived Stem Cells Differentiation into Insulin-Producing Cells

Abstract

Islet cell replacement represents the most promising approach for the treatment of type I diabetes. However, it is limited by a shortage of pancreas donors. Here, we report that human amniotic fluid-derived stem cells (hAFSCs) can be induced to differentiate into functional insulin-producing cells by knocking down neuronal restrictive silencing factor (NRSF). In this study, lentiviral vectors were used to deliver small interference NRSF (siNRSF) RNA into hAFSCs. After infection with lentivirus containing siNRSF, hAFSCs were successfully induced to differentiate into insulin-producing cells. The differentiated siNRSF-hAFSCs expressed genes specific for islet cells, such as Pdx1, Hnf4α, Isl-1, Nkx6.1, Insulin, and Glut2. These cells also produced and released C-peptide in a glucose-responsive manner. These findings indicated that hAFSCs could be induced to differentiate into insulin-producing β-like cells by NRSF silencing.

Long term effects of the implantation of autologous bone marrow mononuclear cells for type 2 diabetes mellitus

“…However, limited availability of islets, high rates of islet graft failure, and the need for life-long non-specific immunosuppressive therapy are major obstacles to the widespread application of this therapeutic approach. Previous studies have shown that several types of stem cells can differentiate into islet insulin-secreting beta-cells [1][2][3] and that these cells can reduce blood glucose levels in animal models. Thus the outcome of such stem cell studies has established the foundation for overcoming DM.…”

Repression of COUP-TFI Improves Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells

“…Recently, many studies have shown that the transcriptional repressors also play a key role in the process of differentiation 21, 22. Several studies have suggested that the suppression of transcriptional repressors can induce mesenchymal stem cell differentiation into IPCs 23, 24. Accordingly, we hypothesize that silencing the expression of transcriptional repressors expressed in bmMSCs can improve differentiation into IPCs.…”

Neuron-restrictive Silencer Factor (NRSF) Represses Cocaine- and Amphetamine-regulated Transcript (CART) Transcription and Antagonizes cAMP-response Element-binding Protein Signaling through a Dual NRSE Mechanism

“…Primers were annealed and cloned under control of the U6 promoter in pSicoR vector. Constructs were verified by DNA sequencing (35). The siRNA mixtures against CoREST, HDAC1, HDAC2, mSin3A, or mSin3B were purchased from Dharmacon.…”