Combined Growth Factor and Gene Therapy: An Approach for Hair Cell Regeneration and Hearing Recovery.

INTRODUCTION: Fibroblast growth factor, nerve growth factor neurotrophins, and insulin-like growth factor 1 are considered 3 families of growth factors that can be involved in the process of otic neurogenesis. In this respect, otic neurons can also be connected with mechanoreceptors in the ear, the hair cells (HCs), as well as the central nervous system. As a growth factor is combined with gene transfer technology, it can be used for hair cell regeneration. Gene therapy can be similarly employed to introduce genes into a system in order to induce the expression of genes for therapeutic agents, to replace defective genes, or to re-program supporting or surrounding cells to acquire the phenotype of lost or damaged cells in order to repair or regenerate the damaged tissue.

OBJECTIVE: The purpose of this review article was to investigate the epigenetic and growth factors involved in the differentiation pathway of embryonic stem cells (ESCs) into HCs and auditory neurons (ANs).

METHODS: To this end, the databases of Directory of Open Access Journals, Google Scholar, PubMed (NLM), LISTA (EBSCO), as well as Web of Science were searched.

RESULTS: Given the results available in the related literature, the differentiation efficacy of ESCs toward the ANs and the HCs, the important role of growth factors, and 3 different strategies of application of miRNA, epigenetic regulation, and preparation of three-dimensional (3D) environments were suggested to be taken into consideration in order to improve these studies in the future. Furthermore, the role of epige-netic mechanisms and miRNA in this differentiation process became quite obvious; hence, the utilization of such procedures in the near future would be significant.

CONCLUSION: Combining several techniques with a synergic effect (such as growth factor gene therapy and 3D environments) seemed to lead to obtaining the best results as a therapeutic strategy.