Polysaccharide hydrogel combined with mesenchymal stem cells promotes the healing of corneal alkali burn in rats.

Yifeng Ke,Yifeng Ke,Xuan Cui,Xuan Cui,Xiaorong Li,Xiaorong Li,Xun Liu,Xun Liu,Min Yu,Chunbo Yang,Chunbo Yang,Yixiang Wu,Neil A Bhowmick

doi:10.1371/journal.pone.0119725

Yifeng Ke, Yifeng Ke + Show 11 more

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https://doi.org/10.1371/journal.pone.0119725

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Abstract

Corneal chemical burns are common ophthalmic injuries that may result in permanent visual impairment. Although significant advances have been achieved on the treatment of such cases, the structural and functional restoration of a chemical burn-injured cornea remains challenging. The applications of polysaccharide hydrogel and subconjunctival injection of mesenchymal stem cells (MSCs) have been reported to promote the healing of corneal wounds. In this study, polysaccharide was extracted from Hardy Orchid and mesenchymal stem cells (MSCs) were derived from Sprague-Dawley rats. Supplementation of the polysaccharide significantly enhanced the migration rate of primarily cultured rat corneal epithelial cells. We examined the therapeutic effects of polysaccharide in conjunction with MSCs application on the healing of corneal alkali burns in rats. Compared with either treatment alone, the combination strategy resulted in significantly better recovery of corneal epithelium and reduction in inflammation, neovascularization and opacity of healed cornea. Polysaccharide and MSCs acted additively to increase the expression of anti-inflammatory cytokine (TGF-β), antiangiogenic cytokine (TSP-1) and decrease those promoting inflammation (TNF-α), chemotaxis (MIP-1α and MCP-1) and angiogenesis (VEGF and MMP-2). This study provided evidence that Hardy Orchid derived polysaccharide and MSCs are safe and effective treatments for corneal alkali burns and that their benefits are additive when used in combination. We concluded that combination therapy with polysaccharide and MSCs is a promising clinical treatment for corneal alkali burns and may be applicable for other types of corneal disorder.

Highlights

Corneal chemical burns are common ophthalmic emergencies accounting for 7.7–18% of all ocular traumas, with alkali injuries being more common than those from acid [1]
We explored the effect of topical polysaccharide therapy in combination with subconjunctival administration of mesenchymal stem cells (MSCs) on the healing of corneal alkali burns
Our study revealed that when used in isolation, polysaccharide and MSC therapy reduced the area of neovascularization to a similar degree and that their effects were additive when used in combination

Summary

Introduction

Corneal chemical burns are common ophthalmic emergencies accounting for 7.7–18% of all ocular traumas, with alkali injuries being more common than those from acid [1]. Polysaccharide and MSCs Promote Healing of Corneal Alkali Burn complications and result from the processes of inflammation, neovascularization, and conjunctivalization of cornea [3,4,5]. Strategies to treat corneal chemical burns include antibiotics, tear substitutes, corticosteroids, ascorbic acid, collagenase inhibitors and surgical treatments such as penetrating keratoplasty and amniotic membrane transplantation [6]. The structural and functional restoration of alkali burn-injuries to the cornea remains a challenge, despite these therapies and prompting the search for novel treatment strategies including the use of polysaccharides and stem cell based therapies

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Conclusion