Transdifferentiation of periodontal ligament-derived stem cells into retinal ganglion-like cells and its microRNA signature

Ng, Tsz Kin; Yung, Jasmine Sum Yee; Choy, Kwong Wai; Cao, Di; Leung, Christopher Kai-Shun; Cheung, Herman S.; Pang, Chi Pui

doi:10.1038/srep16429

Cited by 51 publications

(47 citation statements)

References 43 publications

(69 reference statements)

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“…On the contrary, stem cells from human PDL, are easily accessible, and become an autologous cell source for neural therapy . Human PDLSCs are multipotent in nature and can be induced to differentiate into different lineages, including neuronal lineage . In this study, we demonstrated the PDLSC‐mediated RGC protection in a rat model of ONC.…”

Section: Discussionmentioning

confidence: 62%

“…Human PDLSC lines were previously established and characterized . They were maintained in 1:1 Dulbecco's modified Eagle's medium/F‐12 medium (DMEM/F12; Gibco BRL, Rockville, MD) supplemented with 10% heat‐inactivated fetal bovine serum (Gibco BRL) and 1× penicillin‐streptomycin (P/S; Gibco BRL).…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that stem cells derived from human periodontal ligament (PDL) contains 95% of MSCs and 5% of neural crest stem cells . Human PDL‐derived stem cells (PDLSCs) possess cell replacement potential and can be directed to retinal lineage, especially the electrically functional RGCs . In addition to the transdifferentiation ability, we aimed to explore its neural repair potential.…”

Section: Introductionmentioning

confidence: 99%

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

Cen

Liang

et al. 2018

Stem Cells

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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.

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Section: Discussionmentioning

confidence: 62%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Cen

Liang

et al. 2018

Stem Cells

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“…ARPE-19 cell integrity was examined by the immunofluorescence analysis of tight junction protein (ZO-1) using our previously established protocol44. Briefly, 1 × 10 4 cells per well were seeded on a glass coverslip in a 12-well plate (Corning Life Sciences).…”

Section: Methodsmentioning

confidence: 99%

Continuous exposure to non-lethal doses of sodium iodate induces retinal pigment epithelial cell dysfunction

Zhang

Brelén

et al. 2016

Sci Rep

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Age-related macular degeneration (AMD), characterized by progressive degeneration of retinal pigment epithelium (RPE), is the major cause of irreversible blindness and visual impairment in elderly population. We previously established a RPE degeneration model using an acute high dose sodium iodate to induce oxidative stress. Here we report findings on a prolonged treatment of low doses of sodium iodate on human RPE cells (ARPE-19). RPE cells were treated continuously with low doses (2–10 mM) of sodium iodate for 5 days. Low doses (2–5 mM) of sodium iodate did not reduce RPE cell viability, which is contrasting to cell apoptosis in 10 mM treatment. These low doses are sufficient to retard RPE cell migration and reduced expression of cell junction protein ZO-1. Phagocytotic activity of RPE cells was attenuated by sodium iodate dose-dependently. Sodium iodate also increased expression of FGF-2, but suppressed expression of IL-8, PDGF, TIMP-2 and VEGF. Furthermore, HTRA1 and epithelial-to-mesenchymal transition marker proteins were downregulated, whereas PERK and LC3B-II proteins were upregulated after sodium iodate treatment. These results suggested that prolonged exposure to non-lethal doses of oxidative stress induces RPE cell dysfunctions that resemble conditions in AMD. This model can be used for future drug/treatment investigation on AMD.

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“…Human ocular cell lines, including retinal pigment epithelial (RPE) cells ARPE-19 (catalogue number: CRL-2302, American Type Culture Collection (ATCC), Manassas, VA) [11,12], lens epithelial cells B3 (catalogue number: CRL-11421, ATCC) [13], primary trabecular meshwork (TM) cells [14], and retinoblastoma cells Y79 (catalogue number: HTB-18, ATCC) [15], have been previously established. We also collected human mesenchymal stem cells (MSCs) from different sources, including bone marrow-derived MSCs (BM-MSCs; catalogue number: 7500; ScienceCell Research Laboratories, Carlsbad, CA) [16], adipose-derived stem cells (ASCs) [17], and periodontal ligament-derived stem cells (PDLSCs) [18,19]. Other human tissue cell lines, such as human umbilical vein endothelial cells (HUVEC; catalogue number: CRL-1730, ATCC), lung epithelial carcinoma cells A549 (catalogue number: CCL-185, ATCC), liver hepatocellular carcinoma cells HepG2 (catalogue number: HB-8065, ATCC) and epidermal keratinocytes HaCaT (catalogue number: T0020001, AddexBio, San Diego, CA), were also investigated in this study.…”

Section: Human Cell Lines and Mouse Tissuesmentioning

confidence: 99%

Expression of SARS-CoV-2 receptor ACE2 and TMPRSS2 in human primary conjunctival and pterygium cell lines and in mouse cornea

Chen

Jhanji

et al. 2020

Eye

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197

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Purpose To determine the expressions of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) genes in human and mouse ocular cells and comparison to other tissue cells. Methods Human conjunctiva and primary pterygium tissues were collected from pterygium patients who underwent surgery. The expression of ACE2 and TMPRSS2 genes was determined in human primary conjunctival and pterygium cells, human ocular and other tissue cell lines, mesenchymal stem cells as well as mouse ocular and other tissues by reverse transcription-polymerase chain reaction (RT-PCR) and SYBR green PCR.Results RT-PCR analysis showed consistent expression by 2 ACE2 gene primers in 2 out of 3 human conjunctival cells and pterygium cell lines. Expression by 2 TMPRSS2 gene primers could only be found in 1 out of 3 pterygium cell lines, but not in any conjunctival cells. Compared with the lung A549 cells, similar expression was noted in conjunctival and pterygium cells. In addition, mouse cornea had comparable expression of Tmprss2 gene and lower but prominent Ace2 gene expression compared with the lung tissue. Conclusion Considering the necessity of both ACE2 and TMPRSS2 for SARS-CoV-2 infection, our results suggest that conjunctiva would be less likely to be infected by SARS-CoV-2, whereas pterygium possesses some possibility of SARS-CoV-2 infection. With high and consistent expression of Ace2 and Tmprss2 in cornea, cornea rather than conjunctiva has higher potential to be infected by SARS-CoV-2. Precaution is necessary to prevent possible SARS-CoV-2 infection through ocular surface in clinical practice.

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Transdifferentiation of periodontal ligament-derived stem cells into retinal ganglion-like cells and its microRNA signature

Cited by 51 publications

References 43 publications

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

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

Continuous exposure to non-lethal doses of sodium iodate induces retinal pigment epithelial cell dysfunction

Expression of SARS-CoV-2 receptor ACE2 and TMPRSS2 in human primary conjunctival and pterygium cell lines and in mouse cornea

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