Affiliations: Department of Anatomical Sciences, Tarbiat Modares
University, School of Medical Sciences, Tehran, Iran | Department of Anatomical Sciences, Tarbiat Modares
University, School of Medical Sciences, Tehran, Iran | Shafa Neuroscience Center, Khatam Al-Anbia hospital,
Tehran, Iran
Note: [] Corresponding author: Taki Tiraihi, Department of Anatomical
Sciences, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box
14155-4838, Tehran, Iran. Fax: +98 21 801 6544; E-mail:
[email protected]/[email protected]
Abstract: Bone marrow stromal cells (BMSCs) are multipotent and can be induced
to differentiate into different lineages including osteogenic, chondrogenic,
myogenic and neuronal phenotypes. BMSCs were reported to be a suitable option
for regenerative medical research. In this study, BMSCs were induced into
GABAergic phenotypes using β-mercaptoethanol (βME) and retinoic acid
(RA) as preinducers followed by potassium chloride as inducer, and were
evaluated by fibronectin and Oct-4. The percentages of cells immunoreactive for
nestin, neurofilaments (NF 68, NF 160, and NF 200), GABA and GABA synthesizing
and packaging enzymes (GAD1, GAD2, VGAT) were used for evaluating GABAergic
differentiation. RT-PCR was used for confirming the expression of these
enzymes. The differentiated cells were loaded and unloaded with FM1-43 in order
to assess the functionality of the cells. At the preinduction stage, the cells
downregulated fibronectin and Oct-4, and expressed neuronal markers. At the
induction stage, the preinduced cells transdifferentiated into GABAergic cells,
as confirmed by immunohistochemistry and RT-PCR. The GABAergic cells were
stained and destained with FM1-43. Therefore, the two-stage induction protocol
resulted in transdifferentiation of BMSCs into GABAergic cells with synaptic
release upon stimulation.
Keywords: Rat, BMSCs, GABAergic cells, transdifferentiation, cell therapy
