Differentiation of eye field neuroectoderm from human adipose-derived stem cells by using small-molecules and hADSC-conditioned medium

Abstract

Recently, stem-cell therapy as a promising therapeutic alternative is considered to treat retinal degenerative diseases. Here, we used small molecules and concentrated conditioned medium selectively enriched with Amicon filter units from human adipose-derived stem cells (hADSC-CM) containing various neurotrophic factors to induce hADSCs toward eye field neuroectoderm (EFN). For induction of stem cells, hADSC-CM and small molecules CKI-7, SB431542 and LDN193189 as inhibitors of Wnt, Nodal and BMP4 signaling pathways were used, respectively. We found the highest expression of β-TUB III as a neural marker in the group in which small molecules and conditioned medium were applied simultaneously. Moreover, EFN markers SIX3, PAX6 and RAX had higher expression in the presence of a conditioned medium. However, the superior expression of ENF marker OTX2 was seen in the small molecules group. Our results indicated that neurotrophic factors present in hADSCs-CM could induce hADSCs into EFN cells. Therefore, a more thorough study of these factors and their effects in hADSC-CM might pave the way for cellular and non-cellular therapy in retinal degenerative diseases.

Keywords: Conditioned medium; Eye field; Small-molecules; hADSCs.