Human Ocular Epithelial Cells Endogenously Expressing SOX2 and OCT4 Yield High Efficiency of Pluripotency Reprogramming

Poon, Ming Wai; He, Jia; Xiaowei, Fang; Zhang, Zhao; Wang, Weixin; Wang, Junwen; Qiu, Fangfang; Tse, Hung‐Fat; Li, Wei; Liu, Zuguo; Lian, Qizhou

doi:10.1371/journal.pone.0131288

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…28 Primary hCECs (C018-5c, Life Technologies, Gaithersburg, MD, USA) were cultured according to the published protocol. 29 hCECs were maintained at 37 °C, 5% CO 2 , in Keratinocyte–SFM medium (Cat. No.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage

et al. 2016

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Recent studies have demonstrated that mesenchymal stem cells (MSCs) can donate mitochondria to airway epithelial cells and rescue mitochondrial damage in lung injury. We sought to determine whether MSCs could donate mitochondria and protect against oxidative stress-induced mitochondrial dysfunction in the cornea. Co-culturing of MSCs and corneal epithelial cells (CECs) indicated that the efficiency of mitochondrial transfer from MSCs to CECs was enhanced by Rotenone (Rot)-induced oxidative stress. The efficient mitochondrial transfer was associated with increased formation of tunneling nanotubes (TNTs) between MSCs and CECs, tubular connections that allowed direct intercellular communication. Separation of MSCs and CECs by a transwell culture system revealed no mitochiondrial transfer from MSCs to CECs and mitochondrial function was impaired when CECs were exposed to Rot challenge. CECs with or without mitochondrial transfer from MSCs displayed a distinct survival capacity and mitochondrial oxygen consumption rate. Mechanistically, increased filopodia outgrowth in CECs for TNT formation was associated with oxidative inflammation-activated NFκB/TNFαip2 signaling pathways that could be attenuated by reactive oxygen species scavenger N-acetylcysteine (NAC) treatment. Furthermore, MSCs grown on a decellularized porcine corneal scaffold were transplanted onto an alkali-injured eye in a rabbit model. Enhanced corneal wound healing was evident following healthy MSC scaffold transplantation. And transferred mitochondria was detected in corneal epithelium. In conclusion, mitochondrial transfer from MSCs provides novel protection for the cornea against oxidative stress-induced mitochondrial damage. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.

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Section: Methodsmentioning

confidence: 99%

Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage

et al. 2016

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“…Cells were then harvested for Western Blotting analysis39 using specific antibodies for PIκb (abcam). The housekeeping gene β-actin was used for normalization (abcam).…”

Section: Methodsmentioning

confidence: 99%

“…The housekeeping gene β-actin was used for normalization (abcam). Specific secondary antibodies (1:1000; Dako, USA)3940 were used. Intensity of the bands was quantified using the Image Processing and Analysis in Java (Image J) software (Wayne Rasband.Research Services Branch, National Institute of Mental Health, Bethesda, Maryland, USA).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of NUCKS Facilitates Corneal Recovery Following Alkali Burn

Poon

Jiang

Qin

et al. 2017

Sci Rep

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Corneal wound healing involves a complex cascade of cytokine-controlled cellular events, including inflammatory and angiogenesis responses that are regulated by transcriptional chromatin remodeling. Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate (NUCKS) is a key chromatin modifier and transcriptional regulator of metabolic signaling. In this study, we investigated the role of NUCKS in corneal wound healing by comparing its effects on corneal alkali burn in NUCKS knockout (NKO) and NUCKS wild-type (NWT) mice. Our data showed that following alkali-injury, inhibition of NUCKS (NKO) accelerated ocular resurfacing and suppressed neovascularization; the cytokine profile of alkali burned corneas in NKO mice showed suppressed expression of inflammation cytokines (IL1A & IL1B); upregulated expression of antiangiogenic factor (Pigment Epithelium-derived Factor; PEDF); and downregulated expression of angiogenic factor (Vascular Endothelial Growth Factor, VEGF); in vitro, following LPS-induced NFκB activation, NKO corneal cells showed reduced expression of IL6, IP10 and TNFα. In vitro, corneal epithelial cells showed reduced NF-κb activation on silencing of NUCKS and corresponding NFκB-mediated cytokine expression was reduced. Here, we illustrate that inhibition of NUCKS played a role in cytokine modulation and facilitated corneal recovery. This reveals a potential new effective strategy for ocular burn treatment.

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“…Sox2 has been described as being expressed in many epithelial cell types, including conjunctival epithelial cells. In the conjunctival ocular surface epithelial cells, but not ocular stromal cells, the pluripotent stem cell marker Oct4 has been found expressed [33]. ABCG-2 has a role in the maintenance of retinal stem cells under the regulation of Notch signalling.…”

Section: Discussionmentioning

confidence: 99%

Cultivation and characterization of pterygium as an ex vivo study model for disease and therapy

Josifovska

Szabó

Nagymihály

et al. 2017

Contact Lens and Anterior Eye

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A B S T R A C TPurpose: Development of ex vivo model to study pathogenesis, inflammation and treatment modalities for pterygium. Methods: Pterygium obtained from surgery was cultivated (3 months). Gravitational attachment method using viscoelastic facilitated adherence of graft and outgrowing cells. Medium contained serum as the only growth supplement with no use of scaffolds. Surface profiling of the multi-layered cells for hematopoietic-and mesenchymal stem cell markers was performed. Examination of cells by immunohistochemistry using pluripotency, oxidative stress, stemness, migration and proliferation, epithelial and secretory markers was performed. The effect of anti-proliferative agent Mitomycin C upon secretion of pro-inflammatory cytokines IL-6 and IL-8 was assessed. Results: Cells showed high expression of migration-(CXCR4), secretory-(MUC1, MUC4) and oxidative damage-(8-OHdG) markers, and low expression of hypoxia-(HIF-1α) and proliferation-(Ki-67) markers. Moderate and low expression of the pluripotency markers (Vimentin and ΔNp63) was present, respectively, while the putative markers of stemness (Sox2, Oct4, ABCG-2) and epithelial cell markers-(CK19, CK8-18) were weak. The surface marker profile of the outgrowing cells revealed high expression of the hematopoietic marker CD47, mesenchymal markers CD90 and CD73, minor or less positivity for the hematopoietic marker CD34, mesenchymal marker CD105, progenitor marker CD117 and attachment protein markers while low levels of IL-6 and IL-8 secretion ex vivo, were inhibited upon Mitomycin C treatment. Conclusion: Ex vivo tissue engineered pterygium consists of a mixture of cells of different lineage origin, suitable for use as a disease model for studying pathogenesis ex vivo, while opening possibilities for new treatment and prevention modalities.

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Human Ocular Epithelial Cells Endogenously Expressing SOX2 and OCT4 Yield High Efficiency of Pluripotency Reprogramming

Cited by 9 publications

References 34 publications

Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage

Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage

Inhibition of NUCKS Facilitates Corneal Recovery Following Alkali Burn

Cultivation and characterization of pterygium as an ex vivo study model for disease and therapy

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