Affiliations: Faculty of Medical Sciences, Department of Anatomical Sciences, Tarbiat Modares and Shefa Neuroscience Research Center, Khatam Al-Anbia Hospital, University, Tehran, Iran | Faculty of Medical Sciences, Department of Anatomical Sciences, Tarbiat Modares University and Shefa Neuroscience Research Center, Khatam Al-Anbia, Tehran, Iran | Faculty of Medical Sciences, Department of Clinical Biochemistry, Tarbiat Modares University, Tehran, Iran | Shefa Neuroscience Research Center, Khatam Al-Anbia Hospital, Tehran, Iran
Note: [] Corresponding author: T. Tiraihi, Faculty of Medical Sciences, Department of Anatomical Sciences, Tarbiat Modares University, Tehran 14115-111, Iran. Tel.: +98 21 88011001; Fax: +98 21 88013030; E-mails: takialtr@modares.ac.ir; ttiraihi@gmail.com
Abstract: 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.
