Effects of Growth Factors and the MicroRNA-183 Family on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells Towards Auditory Neuron-Like Cells.

Abstract

Introduction: Hearing Loss (HL) is known as the most common sensory processing disorder across the world. An effective treatment which has been currently used for patients suffering from this condition is cochlear implant (CI). The major limitation of this treatment is the need for a healthy auditory neuron (AN). Accordingly, mesenchymal cells (MCs) are regarded as good candidates for cell-based therapeutic approaches. The present study aimed to investigate the potentials of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) for differentiation towards ANs along with using treatments with growth factors and microRNA (miRNA) transfection in vitro.

Methods: To this end, neurospheres derived from hBM-MSCs were treated via basic fibroblast growth factor (bFGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) as growth factors N2 and B27 supplements, as well as miRNA-96, -182, -183 transfected into hBM-MSCs in order to evaluate the differentiation of such cells into ANs.

Results: Treatments with growth factors demonstrated a significant increase in neurogenin 1 (Ngn1) and sex determining region Y-box 2 (SOX2) markers; but tubulin, microtubule-associated protein 2 (MAP2), and GATA binding protein 3 (GATA3) markers were not statistically significant. The findings also revealed that miRNA-182 expression in miRNA-183 family could boost the expressions of some AN marker (ie, Ngn1, SOX2, peripherin, and nestin) in vitro.

Discussion: It can be concluded that miRNA is probably a good substitute for growth factors used in differentiating into ANs. Transdifferentiation of hBM-MSCs into ANs, which does not occur under normal conditions, may be thus facilitated by miRNAs, especially miRNA-182, or via a combination of miRNA and growth factors.