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

Ling Ping Cen, Tsz Kin Ng, Jia Jian Liang, Xi Zhuang, Xiaowu Yao, Gary Hin Fai Yam, Haoyu Chen, Herman S Cheung, Mingzhi Zhang, Chi Pui Pang

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
JournalStem Cells
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Optic Nerve Injuries
Periodontal Ligament
Retinal Ganglion Cells
Axons
Regeneration
Cell Survival
Stem Cells
Nerve Crush
Optic Nerve Diseases
Cytoprotection
Optic Nerve
Vision Disorders
Brain-Derived Neurotrophic Factor
Inbred F344 Rats
Stem Cell Transplantation
Neuroprotective Agents
Neurites
Blindness
Tubulin
Coculture Techniques

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury. / Cen, Ling Ping; Ng, Tsz Kin; Liang, Jia Jian; Zhuang, Xi; Yao, Xiaowu; Yam, Gary Hin Fai; Chen, Haoyu; Cheung, Herman S; Zhang, Mingzhi; Pang, Chi Pui.

In: Stem Cells, 01.01.2018.

Research output: Contribution to journalArticle

Cen, Ling Ping ; Ng, Tsz Kin ; Liang, Jia Jian ; Zhuang, Xi ; Yao, Xiaowu ; Yam, Gary Hin Fai ; Chen, Haoyu ; Cheung, Herman S ; Zhang, Mingzhi ; Pang, Chi Pui. / Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury. In: Stem Cells. 2018.
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AU - Zhuang, Xi

AU - Yao, Xiaowu

AU - Yam, Gary Hin Fai

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