Concise Review: Stem Cells for Corneal Wound Healing

Saghizadeh, Mehrnoosh; Kramerov, Andrei A.; Svendsen, Clive N.; Ljubimov, Alexander V.

doi:10.1002/stem.2667

Cited by 78 publications

(58 citation statements)

References 88 publications

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“…2 ) as a means to assess the regulation of this cell–cell communication pathway in response to epithelial tissue damage in the eye. 24 , 26 , 29 , 30 During corneal epithelial regeneration, EphA2 immunoreactivity increased throughout the cornea ( Figs. 2 A, 2 C) in a manner that corresponded with elevated EphA2 mRNA transcript levels ( Fig.…”

Section: Resultsmentioning

confidence: 98%

EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling

Kaplan

Ventrella

Han

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeProgenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal–corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal–corneal epithelial boundary organization.MethodsEphA2-expressing corneal epithelial cells engineered to express ephrin-A1 were used to study boundary formation in vitro in a manner that mimicked the relative abundance of these juxtamembrane signaling proteins in the limbal and corneal epithelium in vivo. Interaction of these two distinct cell populations following initial seeding into discrete culture compartments was assessed by live cell imaging. Immunofluoresence and immunoblotting was used to evaluate the contribution of downstream growth factor signaling and cell–cell adhesion systems to boundary formation at sites of heterotypic contact between ephrin-A1 and EphA2 expressing cells.ResultsEphrin-A1–expressing cells impeded and reversed the migration of EphA2-expressing corneal epithelial cells upon heterotypic contact formation leading to coordinated migration of the two cell populations in the direction of an ephrin-A1–expressing leading front. Genetic silencing and pharmacologic inhibitor studies demonstrated that the ability of ephrin-A1 to direct migration of EphA2-expressing cells depended on an a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and epidermal growth factor receptor (EGFR) signaling pathway that limited E-cadherin–mediated adhesion at heterotypic boundaries.ConclusionsEphrin-A1/EphA2 signaling complexes play a key role in limbal–corneal epithelial compartmentalization and the response of these tissues to injury.

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Section: Resultsmentioning

confidence: 98%

EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling

Kaplan

Ventrella

Han

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Mesenchymal stem cells (MSCs) are known to play an important role in tissue repair and maintenance and have been extensively studied for regenerative therapies [4,5]. There is a wealth of evidence from animal studies that the plethora of cytokines and growth factors working in concert within the secreted factors (secretome) of MSCs are able to reduce scarring, neovascularization (NV), and inflammation while promoting epithelialization after injuries [6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier

Fernandes-Cunha

Putra

et al. 2019

Stem Cells Translational Medicine

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Severe corneal injuries often result in permanent vision loss and remain a clinical challenge. Human bone marrow‐derived mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their antiscarring, anti‐inflammatory, and antiangiogeneic properties. We aimed to deliver lyophilized MSC secretome (MSC‐S) within a viscoelastic gel composed of hyaluronic acid (HA) and chondroitin sulfate (CS) as a way to enhance corneal re‐epithelialization and reduce complications after mechanical and chemical injuries of the cornea. We hypothesized that delivering MSC‐S within HA/CS would have improved wound healing effects compared the with either MSC‐S or HA/CS alone. The results showed that a once‐daily application of MSC‐S in HA/CS enhances epithelial cell proliferation and wound healing after injury to the cornea. It also reduced scar formation, neovascularization, and hemorrhage after alkaline corneal burns. We found that combining MSC‐S and HA/CS increased the expression of CD44 receptors colocalized with HA, suggesting that the observed therapeutic effects between the MSC‐S and HA/CS are in part mediated by CD44 receptor upregulation and activation by HA. The results from this study demonstrate a reproducible and efficient approach for delivering the MSC‐S to the ocular surface for treatment of severe corneal injuries. stem cells translational medicine 2019;8:478–489

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“…These CEC-like cells have similar shapes and some characteristics of native HCECs. However, the limitations of the proliferation ability, pump and barrier function, ethical issues, or lack of preclinical studies impedes the potential therapy in clinical applications of these introduced CECs-like cells [ 38 , 39 ]. Therefore, the focus is still on how to improve proliferation and function of HCECs.…”

Section: Discussionmentioning

confidence: 99%

Promoting the expansion and function of human corneal endothelial cells with an orbital adipose-derived stem cell-conditioned medium

et al. 2017

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BackgroundCorneal endothelial dysfunction causes severe impairment of vision. The only solution is corneal transplantation. However, this treatment is hampered by a worldwide shortage of donor corneas. New therapies may replace the conventional donor corneal transplantation alongside the developments in regenerative medicine and tissue engineering, but sufficient functional corneal endothelial cells (CECs) are essential. The aim of this study was to promote the expansion and function of human corneal endothelial cells (HCECs) in vitro and in vivo.MethodsThe phenotypes of human orbital adipose-derived stem cells (OASCs) were detected by flow cytometry and immunofluorescence. HCECs were isolated and cultured using a conditioned medium obtained from OASCs (OASC-CM) in vitro. Related cell markers of HCECs were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunofluorescence. The cell counting kit-8 (CCK-8) assay and the wound healing assay were performed to evaluate the proliferation ability of the cells. The cultured HCECs were then transplanted into rabbit and monkey corneal endothelial dysfunction models by cell injection.ResultsCD29, CD105, CD49e, CD166, and vimentin were highly expressed in cultured human OASCs. The CEC-relative markers zonula occludens-1 (ZO-1), Na+/K+ ATPase, N-cadherin, Col8a2, and SLC4A4 were expressed in HCECs cultured by OASC-CM. The HCECs were able to maintain polygonal cell morphology and good proliferative capacity. In animal experiments, corneal transparency was achieved after the injection of HCECs, which demonstrated the good repair capacity of the cells.ConclusionsThe proliferation abilities of the cells were significantly enhanced, and related functional markers were strongly positive, while HCEC morphology was maintained using OASC-CM. HCECs obtained some stem cell-like properties. This preclinical study confirmed the therapeutic ability of the HCECs in vivo. Our findings demonstrated that cultured HCECs with OASC-CM might be a promising source for research and clinical treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0737-5) contains supplementary material, which is available to authorized users.

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Concise Review: Stem Cells for Corneal Wound Healing

Cited by 78 publications

References 88 publications

EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling

EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling

Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier

Promoting the expansion and function of human corneal endothelial cells with an orbital adipose-derived stem cell-conditioned medium

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