Clinical Pharmacology & Biopharmaceutics
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Neurodegenerative disorders are characterized by chronic and progressive loss of neurons in structure and function related
to aging such as Alzheimer’s disease, the latter characterized by the degeneration of cholinergic neurons in basal forebrain
connected to the cerebral cortex and hippocampus. Amniotic fluid mesenchymal stem cells (AF-MSCs) have been proposed as one of
the candidates for stem cell therapy of nervous system disorders. This study demonstrate that incubation of AF-MSCs, obtained from
16-20 week pregnant women with 10 ng/ml bone morphogenetic protein (BMP)-9 for 48 hours in conditioned medium resulted in
trans-differentiation to cholinergic neuronal-like cells. This phenomenon could also be obtained with N-benzylcinnamide (PT-3).
Pre-treatment for 1 hour with 10 nM PT-3 augmented BMP-9 trans-differentiation effect, elevated βIII-tubulin cell numbers and
fluorescence intensity of immunoreactive ChAT, ameliorated BMP-9-related production of reactive oxygen species and enhanced
anti-apoptosis status of the neuronal-like cells. The trans-differentiation process was accompanied by increased p53 but decreased
Notch1 and SIRT1 (p53 deacetylase) levels and activation of p38, ERK1/2 MAPK and PI3K/Akt pathways, in concert with inactivation
of JNK, all of which were accentuated by PT-3 pre-treatment. These findings suggest that N-benzylcinnamide may not provide a
useful adjuvant in BMP-9-induced trans-differentiation of AFMSCs into ultimately cholinergic neurons.
Wipawan Thangnipon has completed her PhD from UCL Institute of Neurology, London University and Postdoctoral studies from the Marine Biomedical Institute, University of Texas, USA and Institute of Babraham, Cambridge University, UK. She is the Head of Neurochemistry and Tissue Culture Laboratories. She has published more than 35 papers in reputed journals and has been serving as an Editorial Board Member of repute.