Dataset Information

Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth into Retinal Photoreceptor-Like Cells and Their Sustainability In Vivo.

ABSTRACT: Retinal degeneration is characterized by the progressive loss of photoreceptors, and stem cell therapy has become a promising strategy. Many studies have reported that mesenchymal stem cell transplantation can sustain retinal structure and prolong retinal functions based on two mechanisms. One is cell replacement, and the other is the paracrine action of stem cells. Cells from human exfoliated deciduous teeth (SHEDs) show characteristics typical of mesenchymal stem cells. They are derived from the neural crest and are a potential cellular source for neural regeneration in stem cell therapy. In this study, we explored the potential of SHEDs to be induced towards the retinal photoreceptor phenotype and to be sustainable in an animal model of retinal degeneration. A factor-cocktail protocol was used to induce SHEDs towards retinal photoreceptors for 24 days, and the characteristics of the induced cells were identified in terms of morphological changes, biomarker expression and subcellular distribution, and calcium influx. SHEDs were labeled with firefly luciferase for in vivo tracking by bioluminescent imaging and then transplanted into the subretinal space of mice. Our results showed that SHEDs successfully transdifferentiated into photoreceptor-like cells, which displayed neuron-like morphology, and expressed specific genes and proteins associated with retinal precursors, photoreceptor precursors, and mature photoreceptors. In addition, calcium influx was significantly greater in the retinal-induced than in noninduced SHEDs. In vivo tracking confirmed at least 2 weeks of good survival by bioluminescent imaging and 3 months of sustainability of SHEDs by histological analysis. We conclude that SHEDs have the potential to transdifferentiate into retinal photoreceptor-like cells in vitro and maintain good viability in vivo after transplantation into mice with a normal immune system. This demonstrates preliminary success in generating photoreceptor-like cells from SHEDs and applying SHEDs in treating retinal degeneration.

SUBMITTER: Li X

PROVIDER: S-EPMC6393909 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth into Retinal Photoreceptor-Like Cells and Their Sustainability <i>In Vivo</i>.

Li Xiaoxia X Xie Jing J Zhai Yue Y Fang Tengjiaozi T Rao Nanquan N Hu Shuang S Yang Liping L Zhao Yuming Y Wang Yixiang Y Ge Lihong L

Stem cells international 20190214

Retinal degeneration is characterized by the progressive loss of photoreceptors, and stem cell therapy has become a promising strategy. Many studies have reported that mesenchymal stem cell transplantation can sustain retinal structure and prolong retinal functions based on two mechanisms. One is cell replacement, and the other is the paracrine action of stem cells. Cells from human exfoliated deciduous teeth (SHEDs) show characteristics typical of mesenchymal stem cells. They are derived from t ...[more]

PMID: 30906327

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Project description:BackgroundSeveral studies have demonstrated that mesenchymal stem cells can ameliorate the inflammation of allergic rhinitis (AR) and correct the Th1/Th2 immune imbalance.MethodsThis study was performed to explore the immunomodulation properties of stem cells from human exfoliated deciduous teeth (SHEDs) in the treatment of AR in vivo and in vitro. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and then SHEDs or bone marrow mesenchymal stem cells (BMMSCs) were injected intravenously before challenge. We evaluated nasal symptoms, inflammatory infiltration of nasal mucosa, immunoglobulin secretion, cytokine production, and mRNA expression in the spleen. In addition, peripheral blood mononuclear cells (PBMCs) from AR patients were cultured with SHEDs or BMMSCs in the presence of phytohemagglutinin (PHA). PBMCs cultured alone with or without PHA served as controls. After 3?days of culture, we examined the effect of SHEDs on T lymphocyte proliferation, cytokine secretion, and the proportion of Foxp3+ Treg cells via flow cytometry. Finally, to determine the role of soluble factors (TGF-?1, PGE2) in the immunomodulatory mechanism, a cytokine neutralization assay was performed.ResultsNasal symptoms and inflammatory infiltration were significantly reduced after SHED administration. The OVA-specific IgE and IgG1 levels in serum were significantly decreased, and the increased IL-4, IL-5, IL-13, and IL-17A levels in the spleen after OVA challenge were markedly downregulated, while the level of IFN-? was upregulated by SHED administration. The mRNA expression levels also changed correspondingly. SHEDs significantly inhibited the proliferation of T lymphocytes; increased the levels of IFN-?, IL-10, PGE2, and TGF-?1; decreased the levels of IL-4 and IL-17A; and induced the expansion of Treg cells in the coculture system. The neutralization of TGF-?1 partly relieved the immunosuppression of SHEDs, but blocking PGE2 did not. In addition, SHEDs were superior to BMMSCs in inhibiting the Th2 immune response in vivo and inducing the expansion of Treg cells in vitro.ConclusionThese results suggest that SHEDs could correct the CD4+ T cell immune imbalance via Treg cells and may be potential therapeutic agents for the treatment of allergic diseases, such as AR, in the future.

Dataset Information

Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth into Retinal Photoreceptor-Like Cells and Their Sustainability In Vivo.

Publications

Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth into Retinal Photoreceptor-Like Cells and Their Sustainability <i>In Vivo</i>.

Similar Datasets

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