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

Autor(es)

Nery, Arthur A. ^[1] ; Pereira, Ricardo L. ^[1] ; Bassaneze, Vinicius ^[2] ; Nascimento, Isis C. ^[1] ; Sherman, Lauren S. ^[3] ; Rameshwar, Pranela ^[3] ; Lameu, Claudiana ^[1] ; Ulrich, Henning ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo - Brazil

^[3] Rutgers Biomed & Hlth Sci, New Jersey Med Sch, Dept Med, Div Hematol Oncol, Newark, NJ - USA

• Tipo de documento: Artigo Científico
• Fonte: STEM CELL REVIEWS AND REPORTS; v. 15, n. 6, p. 851-863, DEC 2019.
• Citações Web of Science: 1

Resumo

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, alpha 7 nicotinic, M1, M3 and M4 muscarinic acetylcholine, glutamatergic (AMPA2 and mGlu2), purinergic P2Y1 and P2Y4 and GABAergic (GABA-A, beta 3-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 beta 3-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. (AU)

• Processo FAPESP: 12/50880-4 - Células-tronco: dos papéis de receptores de cininas e purinas às aplicações terapêuticas
• Beneficiário: Alexander Henning Ulrich
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/19128-2 - Mecanismos de metástase de tumores infantis para a medula óssea
• Beneficiário: Claudiana Lameu
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
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• Beneficiário: Arthur Andrade Nery
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 08/52334-1 - Reprogramacao de celulas mesenquimais de tecido adiposo humano em celulas-tronco pluripotentes por meio de proteina de fusao tat.
• Beneficiário: Vinícius Bassaneze
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/18730-0 - Identificação e purificação de células-tronco cancerosas de pulmão por aptâmeros de DNA seguida do estudo do sistema calicreína-cininas na progressão tumoral
• Beneficiário: Isis Cristina Corrêa Do Nascimento
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado