Adipocyte. 2019 Dec;8(1):164-177. doi: 10.1080/21623945.2019.1607424.

In vitro transdifferentiation of human adipose tissue-derived stem cells to neural lineage cells - a stage-specific incidence.

Radhakrishnan S^1,2, Trentz OA³, Reddy MS^1,4, Rela M^1,4, Kandasamy M⁵, Sellathamby S².

Abstract

The present Study investigated the intrinsic ability of adipose tissue-derived stem cells (ADSCs) and their neural transdifferentiation in a stage-specific manner. Woodbury's Chemical induction was implemented with modifications to achieve neural transdifferentiation. In Group I, ADSCs were preinduced with β-mercaptoethanol (β-ME) and later, with neural induction medium (NIM). In Group II, ADSCs were directly treated with NIM. In Group III, a DNA methyltransferase (DNMT) inhibitor 5-azacytidine was applied to understand whether transdifferentiation is controlled by epigenetic marks. Irrespective of the presence of (β-ME), the differentiation protocol resulted in glial-lineage cells. Group III produced poorly -differentiated neural cells with neuron-specific enolase positivity. A neuroprogenitor stage (NPC) was identified at d 11 after induction only in Group I. In other groups, this stage was not morphologically distinct. We explored the stage-specific incidence NPC, by alternatively treating them with basic fibroblast growth factor (bFGF), and antioxidants to validate if different signalling could cause varied outcomes (Group IV). They differentiated into neurons, as defined by cell polarity and expression of specific proteins. Meanwhile, neuroprogenitors exposed to NIM (Group I) produced glial-lineage cells. Further refinement and study of the occurrence and terminal differentiation of neuroprogenitors would identify a promising source for neural tissue replacement.