Directed differentiation of human adipose tissue-derived stem cells to dopaminergic neurons in low-serum and serum-free conditions.

Directing the fate of mesenchymal stem cells (MSCs) to dopaminergic neurons has great importance in both biomedical studies and cell therapy of Parkinson's disease. We recently generated dopamine-secreting cells from human adipose tissue-derived stem cells (hADSCs) by exposing the cells to a growth factor cocktail composed of SHH, bFGF, FGF8 and BDNF in low-serum condition. In the current study, we induced the cells by the same dopaminergic inducing cocktail in serum-free B27-supplemented Neurobasal medium. ADSCs differentiated in both conditions expressed several neuronal and dopaminergic markers. However, there were higher gene expression levels under the serum-free condition. Higher levels of TUJ1 and TH proteins were also detected in the cells exposed to the dopaminergic-inducing cocktail under serum-free Neurobasal condition. TH protein was expressed in about 28% and 60% of the cells differentiated in the low-serum and serum-free Neurobasal media, respectively. Moreover, the cells exposed to the dopaminergic-inducing cocktail in the serum-free Neurobasal condition released a more significant amount of dopamine in response to KCl-induced depolarization. Altogether, these findings show a greater efficiency of the serum-free Neurobasal condition for growth factor-directed differentiation of hADSCs to functional dopamine-secreting cells which may be valuable for transplantation therapy of Parkinson's disease in future.