Prospects of Stem Cells for Retinal Diseases

Ng, Tsz Kin; Lam, Dennis S.C.; Cheung, Herman S.

doi:10.1097/apo.0b013e31827e3e5d

Cited by 8 publications

(6 citation statements)

References 67 publications

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“…Stem cells have been studied to restore optic neuropathies . Different stem cell sources, including embryonic stem cells, oligodendrocyte precursor cells as well as bone marrow‐derived and umbilical cord blood‐derived mesenchymal stem cells (MSCs), have been evaluated for their efficacy to promote neural repair and regeneration of central and peripheral nervous systems .…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…Stem cell therapy is a viable regenerative option for CNS disorders (Ng, Fortino, Pelaez, & Cheung, ). On the basis of their self‐renewal properties, cell replacement therapy has been proposed, which hypothesizes that unlimited number of neuronal and glial cells could be synthesized from a given stem cell source to substitute the diseased/injured cells in the affected tissues (Ng, Lam, & Cheung, ). This theory is mainly established from the pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, as they can differentiate into the cells of all three germ layers, including the neuronal cells.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐132 directs human periodontal ligament‐derived neural crest stem cell neural differentiation

Yang

Fortino

et al. 2018

J Tissue Eng Regen Med

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Neurogenesis is the basis of stem cell tissue engineering and regenerative medicine for central nervous system (CNS) disorders. We have established differentiation protocols to direct human periodontal ligament-derived stem cells (PDLSCs) into neuronal lineage, and we recently isolated the neural crest subpopulation from PDLSCs, which are pluripotent in nature. Here, we report the neural differentiation potential of these periodontal ligament-derived neural crest stem cells (NCSCs) as well as its microRNA (miRNA) regulatory mechanism and function in NCSC neural differentiation. NCSCs, treated with basic fibroblast growth factor and epidermal growth factor-based differentiation medium for 24 days, expressed neuronal and glial markers (βIII-tubulin, neurofilament, NeuN, neuron-specific enolase, GFAP, and S100) and exhibited glutamate-induced calcium responses. The global miRNA expression profiling identified 60 upregulated and 19 downregulated human miRNAs after neural differentiation, and the gene ontology analysis of the miRNA target genes confirmed the neuronal differentiation-related biological functions. In addition, overexpression of miR-132 in NCSCs promoted the expression of neuronal markers and downregulated ZEB2 protein expression. Our results suggested that the pluripotent NCSCs from human periodontal ligament can be directed into neural lineage, which demonstrate its potential in tissue engineering and regenerative medicine for CNS disorders.

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“…Reliable strategy to form PDL-like structures is critical in regenerative medicine7. Recently, stem cell engineering offers great promises8.…”

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confidence: 99%

Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials

Huang

Cao

et al. 2015

Sci Rep

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Cigarette smoking contributes to the development of destructive periodontal diseases and delays its healing process. Our previous study demonstrated that nicotine, a major constituent in the cigarette smoke, inhibits the regenerative potentials of human periodontal ligament-derived stem cells (PDLSC) through microRNA (miRNA) regulation. In this study, we hypothesized that the delayed healing in cigarette smokers is caused by the afflicted regenerative potential of smoker PDLSC. We cultured PDLSC from teeth extracted from smokers and non-smokers. In smoker PDLSC, we found significantly reduced proliferation rate and retarded migration capabilities. Moreover, alkaline phosphatase activity, calcium deposition and acidic polysaccharide staining were reduced after BMP2-induced differentiation. In contrast, more lipid deposition was observed in adipogenic-induced smoker PDLSC. Furthermore, two nicotine-related miRNAs, hsa-miR-1305 (22.08 folds, p = 0.040) and hsa-miR-18b (15.56 folds, p = 0.018), were significantly upregulated in smoker PDLSC, suggesting these miRNAs might play an important role in the deteriorative effects on stem cells by cigarette smoke. Results of this study provide further evidences that cigarette smoking affects the regenerative potentials of human adult stem cells.

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Prospects of Stem Cells for Retinal Diseases

Cited by 8 publications

References 67 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

MicroRNA‐132 directs human periodontal ligament‐derived neural crest stem cell neural differentiation

Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials

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