TY - JOUR
T1 - Induction of bone marrow stromal cells into GABAergic neuronal phenotype using creatine as inducer
AU - Mohammad-Gharibani, Payam
AU - Tiraihi, Taki
AU - Mesbah-Namin, Seyed Alireza
AU - Arabkheradmand, Jalil
AU - Kazemi, Hadi
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012
Y1 - 2012
N2 - Purpose: Deficits involving GABAergic neurons have been reported in aging, central nervous trauma and neurodegenerative disorders; bone marrow stromal cells (BMSCs) have been proposed as a feasible source of donor cells in replacement cell therapy. In this study, the effects of creatine on transdifferentiating BMSCs into GABAergic-like neurons were evaluated in vitro. Methods: The BMSCs were isolated from adult rats, preinduced by β-mercaptoethanol (BME) and retinoic acid (RA), and then induced by creatine into GABAergic-like neurons. The cells were characterized using different differentiation markers. The functionality of the differentiated cells was evaluated using FM1-43. Results: The isolated cells expressed Oct-4 and were immunoreactive to fibronectin and CD44. The highest percentages of cells immunoreactive to nestin and neurofilament-68 were found at the second day of preinduction. At the induction stage, there were increases in the number of cells immunoreactive to neurofilament-200, MAP-2, synapsin I, synaptophysin, and NeuN. The percentages of the immunoreactive cells to GABAergic neuron markers increased. The optimal induction dose was 5 mM. The dose of 10 mM showed a decline in the expression of most of these markers. The functionality test indicated that the synaptic vesicles were released upon stimulation. Conclusion: Creatine can induce the differentiation of BMSCs to the GABAergic neuronal phenotype within one week.
AB - Purpose: Deficits involving GABAergic neurons have been reported in aging, central nervous trauma and neurodegenerative disorders; bone marrow stromal cells (BMSCs) have been proposed as a feasible source of donor cells in replacement cell therapy. In this study, the effects of creatine on transdifferentiating BMSCs into GABAergic-like neurons were evaluated in vitro. Methods: The BMSCs were isolated from adult rats, preinduced by β-mercaptoethanol (BME) and retinoic acid (RA), and then induced by creatine into GABAergic-like neurons. The cells were characterized using different differentiation markers. The functionality of the differentiated cells was evaluated using FM1-43. Results: The isolated cells expressed Oct-4 and were immunoreactive to fibronectin and CD44. The highest percentages of cells immunoreactive to nestin and neurofilament-68 were found at the second day of preinduction. At the induction stage, there were increases in the number of cells immunoreactive to neurofilament-200, MAP-2, synapsin I, synaptophysin, and NeuN. The percentages of the immunoreactive cells to GABAergic neuron markers increased. The optimal induction dose was 5 mM. The dose of 10 mM showed a decline in the expression of most of these markers. The functionality test indicated that the synaptic vesicles were released upon stimulation. Conclusion: Creatine can induce the differentiation of BMSCs to the GABAergic neuronal phenotype within one week.
KW - BMSCs
KW - GABAergic-like neurons
KW - creatine
KW - induction
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U2 - 10.3233/RNN-2012-100155
DO - 10.3233/RNN-2012-100155
M3 - Article
C2 - 22903159
AN - SCOPUS:84872147176
SN - 0922-6028
VL - 30
SP - 511
EP - 525
JO - Restorative Neurology and Neuroscience
JF - Restorative Neurology and Neuroscience
IS - 6
ER -