Efficient Generation of Functionally Active Spinal Cord Neurons from Spermatogonial Stem Cells.

Abstract:

:Neural stem cells (NSCs) are hitherto regarded as perspective candidates for cell transplantation in clinical therapies for multilevel spinal cord injury and function restoration. However, the extreme drawbacks of NSCs available for injury transplantation still represent a significant bottleneck in neural regeneration medicine. Therefore, it is essential to establish a suitable cell reservoir as an issue-free alternative. Here, we demonstrate that spermatogonial stem cells (SSCs) derived from rat testis robustly give rise to terminally differentiated, functionally mature spinal cord neurons by using an optimized differentiation protocol. After performing a 3-week in vitro differentiation procedure, most cells exhibited neural morphological features and were Tuj-1 positive. Of note, approximately 60 % of the obtained cells coexpressed choline acetyltransferase (CHAT), acetylcholinesterase (AchE), and calcitonin gene-related peptide (CGRP). More importantly, apart from acquisition of neural antigenic and biochemical properties, nearly all neurons efficiently exhibited in vitro functionality similar to wild-type neurons, such as synapse formation, increased neuronal calcium influx, and electrophysiology. This is the first report revealing consistent and reproducible generation of large amounts of functional neurons from SSCs. Collectively, this system is suitable for studies of SSC transdifferentiation into neuronal cells and can provide sufficient neurons for the treatment of spinal cord injury as well as for genetic and small molecule screenings.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Yang H,Liu C,Chen B,An J,Zhang R,Zhang Q,Zhao J,He B,Hao DJ

doi

10.1007/s12035-016-0057-2

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

788-803

issue

1

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-016-0057-2

journal_volume

54

pub_type

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