Induction of bone marrow stromal cells into GABAergic neuronal phenotype using creatine as inducer

Payam Mohammad-Gharibani, Taki Tiraihi, Seyed Alireza Mesbah-Namin, Jalil Arabkheradmand, Hadi Kazemi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)511-525
Number of pages15
JournalRestorative Neurology and Neuroscience
Volume30
Issue number6
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

Keywords

  • BMSCs
  • GABAergic-like neurons
  • creatine
  • induction

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

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