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Mol Neurobiol. 2017 Sep;54(7):5676-5682. doi: 10.1007/s12035-016-0097-7. Epub 2016 Sep 19.

Differentiation of Spermatogonia Stem Cells into Functional Mature Neurons Characterized with Differential Gene Expression.

Author information

1
Department of Anatomy and Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. bojnordi@modares.ac.ir.
2
Molecular and Cell Biology Research Center, Department of Anatomy and Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, P.O. Box: 48471-91971, Sari, Iran. bojnordi@modares.ac.ir.
3
Department of Biotechnology, Amol University of Special Modern Technologies, P.O. Box 4615863111, Amol, Iran.
4
Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany.
5
Department of Anatomy, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
6
Neuroscience Research Center, Babol University Medical of Sciences, Babol, Iran.
7
Department of Physiology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
8
Department of Anatomy and Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. hatefdr@gmail.com.
9
Immunogenetic Research Center, Department of Anatomy and Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. hatefdr@gmail.com.

Abstract

Transplantation of embryonic stem cells (ESCs) is a promising therapeutic approach for the treatment of neurodegenerative diseases. However, ESCs are not usable clinically due to immunological and ethical limitations. The identification of an alternative safe cell source opens novel options via autologous transplantation in neuro-regeneration circumventing these problems. Here, we examined the neurogenic capacity of embryonic stem-like cells (ES-like cells) derived from the testis using neural growth factor inducers and utilized them to generate functional mature neurons. The neuronal differentiation of ES-like cells is induced in three stages. Stage 1 is related to embryoid body (EB) formation. To induce neuroprogenitor cells, EBs were cultured in the presence of retinoic acid, N2 supplement and fibroblast growth factor followed by culturing in a neurobasal medium containing B27, N2 supplements for additional 10 days, to allow the maturation and development of neuronal progenitor cells. The neurogenic differentiation was confirmed by immunostaining for markers of mature neurons. The differentiated neurons were positive for Tuj1 and Tau1. Real-time PCR dates indicated the expression of Nestin and Neuro D (neuroprogenitor markers) in induced cells at the second stage of the differentiation protocol. The differentiated mature neurons exhibited the specific neuron markers Map2 and β-tubulin. The functional maturity of neurons was confirmed by an electrophysiological analysis of passive and active neural membrane properties. These findings indicated a differentiation capacity of ES-like cells derived from the testis to functionally mature neurons, which proposes them as a novel cell source for neuroregenerative medicine.

KEYWORDS:

Differentiation; Embryonic stem cells; Mature neurons; Neuroregenerative medicine; Spermatogonia stem cells

PMID:
27644129
DOI:
10.1007/s12035-016-0097-7
[Indexed for MEDLINE]

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