Short‐term results of acellular porcine corneal stroma keratoplasty for herpes simplex keratitis

Zheng, Jiao; Huang, Xiaodan; Zhang, Yue; Wang, Yi; Qin, Qiyu; Lin, Lin; Jin, Xiuming; Lam, C. S.; Zhang, Jinnan

doi:10.1111/xen.12509

Cited by 42 publications

(60 citation statements)

References 25 publications

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“…Although ambitious, these goals are within reach given the current pace in the development of corneal regenerative technologies and the parallel developments in clinical evaluation and regulatory approvals of advanced therapeutic modalities. Integration with host stroma [28][29][30] Acellular porcine corneal stroma Abundant, low cost, thick stromal tissue Integration with rabbit stroma, host cells in scaffold 35,38 No evidence provided 39,40 Recellularized scaffolds Cells can actively effect stromal repair Human embryonic stem cells Pluripotent, high proliferative potential…”

Section: Discussionmentioning

confidence: 99%

“…In another Chinese study, acellular porcine corneal stroma was used in lamellar keratoplasty to treat 13 patients for herpes simplex keratitis. 40 After a mean of 15 months of postoperative follow-up, seven cases had mostly transparent corneas but 11 of 13 cases had neovascularization, with graft melting occurring in three cases. Currently, a prospective clinical trial is ongoing in Guangzhou, using the acellular porcine cornea as a deep anterior lamellar graft in cases of infective keratitis.…”

Section: Human Donor Stromal Lenticulesmentioning

confidence: 97%

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Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Lagali

2019

Current Eye Research

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The corneal stroma comprises 90% of the corneal thickness and is critical for the cornea's transparency and refractive function necessary for vision. When the corneal stroma is altered by disease, injury, or scarring, however, an irreversible loss of transparency can occur. Corneal stromal pathology is the cause of millions of cases of blindness globally, and although corneal transplantation is the standard therapy, a severe global deficit of donor corneal tissue and eye banking infrastructure exists, and is unable to meet the overwhelming need. An alternative approach is to harness the endogenous regenerative ability of the corneal stroma, which exhibits self-renewal of the collagenous extracellular matrix under appropriate conditions. To mimic endogenous stromal regeneration, however, is a challenge. Unlike the corneal epithelium and endothelium, the corneal stroma is an exquisitely organized extracellular matrix containing stromal cells, proteoglycans and corneal nerves that is difficult to recapitulate in vitro. Nevertheless, much progress has recently been made in developing stromal equivalents, and in this review the most recent approaches to stromal regeneration therapy are described and discussed. Novel approaches for stromal regeneration include human or animal corneal and/or non-corneal tissue that is acellular or is decellularized and/or recellularized, acellular bioengineered stromal scaffolds, tissue adhesives, 3D bioprinting and stromal stem cell therapy. This review highlights the techniques and advances that have achieved first clinical use or are close to translation for eventual therapeutic application in repairing and regenerating the corneal stroma, while the potential of these novel therapies for achieving effective stromal regeneration is discussed. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Section: Human Donor Stromal Lenticulesmentioning

confidence: 97%

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Lagali

2019

Current Eye Research

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“…Decellularized porcine corneas have been used to treat patients suffering from corneal ulcers 2,3,21 showing the feasibility of employing xenogeneic material. The use of discarded tissue from myopia correction procedures is an option to use human material 6,27 as well as donated corneas unsuitable for transplantation due to low endothelial cell count, for example.…”

Section: Discussionmentioning

confidence: 99%

“…Decellularized porcine corneas have been transplanted into humans in cases of infectious ulcers with encouraging results. 2,3 However, these acellular scaffolds are composed of densely packed collagen lamellae, and thus recellularization is difficult, making it slow, both in vitro 4 and in vivo. 5 In attempts to improve recellularization, human lenticules extracted during myopia correction surgeries have been attached together using a fibrin glue hydrogel to prepare a decellularized scaffold.…”

Section: Introductionmentioning

confidence: 99%

Engineering a Corneal Stromal Equivalent Using a Novel Multilayered Fabrication Assembly Technique

Fernández‐Pérez

Madden

Ahearne

2020

Tissue Engineering Part A

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To overcome the serious shortage of donor corneas for transplantation, alternatives based on tissue engineering need to be developed. Decellularized corneas are one potential alternative, but their densely packed collagen architecture inhibits recellularization in vitro. Therefore, a new rapid method of recellularizing these constructs to ensure high cellularity throughout the collagen scaffold is needed. In this study, we developed a novel method for fabricating corneal constructs by using decellularized porcine corneal sheets assembled using a bottom-up approach by layering multiple sheets between cell-laden collagen I hydrogel. Corneal lenticules were cut from porcine corneas by cryosectioning, then decellularized with detergents and air-dried for storage as sheets. Human corneal stromal cells were encapsulated in collagen I hydrogel and cast between the dried sheets. Constructs were cultured in serum-free medium supplemented with ascorbic acid and insulin for 2 weeks. Epithelial cells were then seeded on the surface and cultured for an additional week. Transparency, cell viability, and phenotype were analyzed by qPCR, histology, and immunofluorescence. Constructs without epithelial cells were sutured onto an ex vivo porcine cornea and cultured for 1 week. Lenticules were successfully decellularized, achieving dsDNA values of 13-1.2 ng/mg dry tissue, and were more resistant to degradation than the collagen I hydrogels. Constructs maintained high cell viability with a keratocyte-like phenotype with upregulation of keratocan, decorin, lumican, collagen I, ALDH3A1, and CD34 and the corneal epithelial cells stratified with a cobblestone morphology. The construct was amenable to surgical handling and no tearing occurred during suturing. After 7 days ex vivo, constructs were covered by a neoepithelium from the host porcine cells and integration into the host stroma was observed. This study describes a novel approach toward fabricating anterior corneal substitutes in a simple and rapid manner, obtaining mature and suturable constructs using only tissue-derived materials.

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“…9 Zheng et al provide much needed details on new factors discovered, such as pre-surgical inflammation, and potential correlations with complications. 9 Similarly, corneal blindness from endothelium dysfunction may be reversed with transplantation of tissue-engineered human corneal endothelium (TE-HCE) grafts. 10 Zhao et al provide insight on the historic limitations of HCE grafts, generating excitement for recent advancements.…”

Section: Throug H the E Ye S Of Xenotr Ans Pl Antationmentioning

confidence: 99%