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Stem Cells. 2018 Jun;36(6):844-855. doi: 10.1002/stem.2812. Epub 2018 Mar 7.

Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury.

Author information

1
Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, People's Republic of China.
2
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
3
Dentistry Department, Second Affiliated Hospital, Shantou University Medical College, Shantou, People's Republic of China.
4
Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, Florida, USA.

Abstract

Optic neuropathies are the leading cause of irreversible blindness and visual impairment in the developed countries, affecting more than 80 million people worldwide. While most optic neuropathies have no effective treatment, there is intensive research on retinal ganglion cell (RGC) protection and axon regeneration. We previously demonstrated potential of human periodontal ligament-derived stem cells (PDLSCs) for retinal cell replacement. Here, we report the neuroprotective effect of human PDLSCs to ameliorate RGC degeneration and promote axonal regeneration after optic nerve crush (ONC) injury. Human PDLSCs were intravitreally injected into the vitreous chamber of adult Fischer rats after ONC in vivo as well as cocultured with retinal explants in vitro. Human PDLSCs survived in the vitreous chamber and were maintained on the RGC layer even at 3 weeks after ONC. Immunofluorescence analysis of βIII-tubulin and Gap43 showed that the numbers of surviving RGCs and regenerating axons were significantly increased in the rats with human PDLSC transplantation. In vitro coculture experiments confirmed that PDLSCs enhanced RGC survival and neurite regeneration in retinal explants without inducing inflammatory responses. Direct cell-cell interaction and elevated brain-derived neurotrophic factor secretion, but not promoting endogenous progenitor cell regeneration, were the RGC protective mechanisms of human PDLSCs. In summary, our results revealed the neuroprotective role of human PDLSCs by strongly promoting RGC survival and axonal regeneration both in vivo and in vitro, indicating a therapeutic potential for RGC protection against optic neuropathies. Stem Cells 2018;36:844-855.

KEYWORDS:

Axon regeneration; Ganglion cells; Optic nerve injuries; Periodontal ligament stem cells; Retina

PMID:
29476565
DOI:
10.1002/stem.2812

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