22-hydroxycholesterol leads to efficient dopaminergic specification of human Mesenchymal Stem Cells

Abstract

In the current study, we aim to investigate the neurogenic effect of 22 (R)- hydroxycholesterol (22-HC), on hMSCs obtained from bone marrow, adipose tissue and dental pulp. The effect was evaluated on the basis of detailed morphological and morphometric analysis, expression of genes and proteins associated with maturation of neurons (NF, MAP2, TUJ1, TH), channel ion proteins (Kv4.2 & SCN5A), chemical functionality (DAT), synapse forming tendency of neurons (Synaptophysin) and transcription factors (ngn2 & Pitx3), efficiency of generation of dopaminergic neurons and functional assessment. The percentage of non- DA cells generation (Ach, TPH2, S100 and GFAP positive cells) was also evaluated to confirm selective neurogenic potential of 22-HC. Post analysis, it was observed that 22-HC yields higher percentage of functional DA neurons and has differential effect on various tissue- specific primary human MSCs. This study, which is one of its kinds, may help in improvising the approach of cell based treatment regimes and drug testing in pharmaceutical industry for Parkinsons disease.