Combination of Chemical and Neurotrophin Stimulation Modulates Neurotransmitter Receptor Expression and Activity in Transdifferentiating Human Adipose Stromal Cells

• Published in: Stem cell reviews and reports Vol. 15; no. 6; pp. 851 - 863
• Main Authors: Nery, Arthur A., Pereira, Ricardo L., Bassaneze, Vinicius, Nascimento, Isis C., Sherman, Lauren S., Rameshwar, Pranela, Lameu, Claudiana, Ulrich, Henning
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2019; Springer Nature B.V
• Subjects: Acetylcholine receptors (muscarinic); ASCL1 protein; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Cell Biology; Coding; Gene expression; Glutamatergic transmission; Glutamic acid receptors (ionotropic); Glutamic acid receptors (metabotropic); Ion currents; Life Sciences; Mesenchymal stem cells; N-Methyl-D-aspartic acid receptors; Neurogenesis; Neurotransmission; Neurotrophic factors; Nitric-oxide synthase; Phenotypes; Regeneration; Regenerative Medicine/Tissue Engineering; Stem Cells; Stromal cells; Therapeutic applications; Tubulin; γ-Aminobutyric acid receptors; Neuronal differentiation; Adipose stromal cells; Transdifferentiation; Human lipoaspirate; Mesenchymal stem cells
• ISSN: 2629-3269; 2629-3277
• DOI: 10.1007/s12015-019-09915-1

Adipose stromal cells are promising tools for clinical applications in regeneration therapies, due to their ease of isolation from tissue and its high yield; however, their ability to transdifferentiate into neural phenotypes is still a matter of controversy. Here, we show that combined chemical and neurotrophin stimulation resulted in neuron-like morphology and regulated expression and activity of several genes involved in neurogenesis and neurotransmission as well as ion currents mediated by NMDA and GABA receptors. Among them, expression patterns of genes coding for kinin-B1 and B2, α7 nicotinic, M1, M3 and M4 muscarinic acetylcholine, glutamatergic (AMPA2 and mGlu2), purinergic P2Y1 and P2Y4 and GABAergic (GABA-A, β3-subunit) receptors and neuronal nitric oxide synthase were up-regulated compared to levels of undifferentiated cells. Simultaneously, expression levels of P2X1, P2X4, P2X7 and P2Y6 purinergic and M5 muscarinic acetylcholine receptors were down-regulated. Agonist-induced activity levels of the studied receptor classes also augmented during neuronal transdifferentiation. Transdifferentiated cells expressed high levels of neuronal β3-tubulin, NF-H, NeuN and MAP-2 proteins as well as increased ASCL1, MYT1 and POU3F2 gene expression known to drive neuronal fate determination. The presented work contributes to a better understanding of transdifferentiation induced by neurotrophins for a prospective broad spectrum of medical applications.