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Periodontal Ligament Stem Cells - A New and Effective means to Treat Optic Nerve Injury?

Review of “Human Periodontal Ligament‐Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Injury” from STEM CELLS by Stuart P. Atkinson

The apoptosis of mature retinal ganglion cells (RGCs) associated with optic nerve (ON) injury inhibits the regeneration of damaged axons [1], leading to irreversible visual impairment and even blindness; however, stem cell-based treatment strategies have the potential to reverse these pathologies [2]. Previous studies from the labs of Chi Pui Pang and Mingzhi Zhang (Shantou University/Chinese University of Hong Kong, PR China) described the application of mesenchymal stem cell-like cells derived from human periodontal ligament (PDLSCs) for retinal cell replacement [3, 4]. In their new STEM CELLS report, Cen et al. assess whether human PDLSCs also enhance RGC survival and stimulate the regeneration of axons in a rat model of optic nerve injury [5].

Three weeks after the injection of human PDLSCs into the vitreous body of adult Fischer rat eyes after an optic nerve crush (ONC) injury, the authors observed surviving cells as floating clusters, while some localized to the nerve fiber layer and the RGC layer. Encouragingly, retinas of PDLSC-treated mice exhibited macrophage infiltration and an inflammatory response concomitant with an increase in RGC survival and axonal regeneration with no signs of tumorigenic growth.

To confirm the in vivo findings, the study moved in vitro to retinal explant cocultures, where the presence of PDLSCs enhanced both RGC survival and neurite regeneration. Interestingly, these experiments suggested that cell-cell interactions and an increase in the secretion of brain‐derived neurotrophic factor (BDNF) acted as the RGC protective mechanisms of human PDLSCs, and not endogenous progenitor cell regeneration.

The authors hope that these new results will promote the study of PDLSC transplantation and RGC protection in patients with optic nerve injuries. However, they also underlined the requirement for additional studies regarding PDLSC-macrophage interactions, longer-term PDLSC survival, and the mechanisms controlling BDNF secretion.

For more periodontal ligament stem cell-based studies and new stem cell therapies for optic nerve injury, stay tuned to the Stem Cells Portal.


  1. Berkelaar M, Clarke D, Wang Y, et al., Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats. The Journal of Neuroscience 1994;14:4368-4374.
  2. Ng TK, Lam DS, and Cheung HS, Prospects of Stem Cells for Retinal Diseases. Asia Pac J Ophthalmol (Phila) 2013;2:57-63.
  3. Huang L, Liang J, Geng Y, et al., Directing Adult Human Periodontal Ligament–Derived Stem Cells to Retinal Fate. Investigative Ophthalmology & Visual Science 2013;54:3965-3974.
  4. Ng TK, Yung JSY, Choy KW, et al., Transdifferentiation of periodontal ligament-derived stem cells into retinal ganglion-like cells and its microRNA signature. Scientific Reports 2015;5:16429.
  5. Cen LP, Ng TK, Liang JJ, et al., Human Periodontal Ligament‐Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury. STEM CELLS 2018;36:844-855.