Eoigenetic remodeling of mesenchymal stem \ncell (msc), by targeting specific micrornas to \ninduce long term neurogenesis: an in vitro \nanalysis of msc plasticity
Year: 2015
Type: book
Abstract: Recently, there has been an increasing interest in MSCs plasticity and their potential to transdifferentiate into neural \nlineages. To have an in-depth understanding of optimal transdifferentiation and its microenvironment, we have \ntransdifferentiated MSCs in different combinatorial treatment of growth factors. Based on previous studies about the \nroles of IGF-1 in the laboratory, we hypothesized that IGF-1 can provide an optimal microenvironment for long-term \nmaintenance and efficient neural induction. Here, we also analysed the roles of differential microRNAs in the \ntransdifferentiation of MSC into neural lineage in the presence of IGF-1. Neuronal induction was carried under four \ndifferent micorenvironments: (A) EGF/bFGF, (B) EGF/bFGF/IGF, (C) EGF/bFGF/LIF, (D) EGF/bFGF/BDNF and (E) \nwithout growth factor as negative control. Neurospheres formed were characterized by immunofluorescence staining \nagainst nestin and the expression was measured by flow cytometry. The cell proliferation and apoptosis was also \nstudied by MTS and Annexin V assay respectively at three different time intervals (24 hours, Day 3 and Day 5). All \ngroups showed significant higher in nestin expression as compared to negative control group. Interestingly, IGF-1 \ntreated group shows better enhancement in cell proliferation and cell survival efficiency. To delineate the exact miRNA \nsignatures in IGF-1 treated sample, we performed miRNAs profiling and analyzed using Genespring software. Among \nthe 2t miRNAs differentially expressed, let-7b, miR-18ta, and miR-26a were found to be specially espressed in IGF-1 \ntreated group. All of them are involved in apoptosis suppression, improve cell proliferation and promote neuronal \ndifferentiation. Our results demonstrate that IGF-1 enhanced cell proliferation and suppressed cell death by triggering \nthe expression of specific miRNAs. This information will be beneficial for improving both cell-based and cell-free \ntherapy of neurodegenerative diseases in the long run.
Author: Hasnan, Jaafar
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7028329966