Reducing porcine corneal graft rejection, with an emphasis on porcine endogenous retrovirus transmission safety: a review

Song, Yaowen; Pan, Zhiqiang

doi:10.18240/ijo.2019.02.21

Cited by 6 publications

(4 citation statements)

References 74 publications

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“…Attempts have been made to produce transgenic pigs expressing cytotoxic T cell antigen 4, responsible for inhibiting T-cell activity, but the genetically modified pigs died prematurely from other infection or vascular rejection causes. 44 , 46 The production of class I major histocompatibility complex knockout pigs using guide RNAs and the Cas9 gene editing technique, as well as reducing the expression of class II swine leukocyte antigen through expression of the human dominant-negative mutant class II transactivator transgene, have been tried. 47 , 48 The initial results of these approaches were promising, as the genetically engineered pigs exhibited normal development despite reduced levels of CD8 + and CD4 + T cells.…”

Section: Immunologic and Technical Barriersmentioning

confidence: 99%

Cardiac Xenotransplantation

Boulet

Cunningham²,

Mehra³

2022

JACC: Basic to Translational Science

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Section: Immunologic and Technical Barriersmentioning

confidence: 99%

Cardiac Xenotransplantation

Boulet

Cunningham²,

Mehra³

2022

JACC: Basic to Translational Science

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“…Various corneal conditions, including keratitis of diverse origins, endothelial dystrophy, keratoconus, ulcers, stem cell deficiencies and other lesions, can result in corneal dysfunction. In the realm of scientific inquiry, whether investigating disease pathogenesis, pharmacokinetics, preclinical neuroscience, elucidating the mechanisms of disease development, training for surgical procedures, devising novel therapeutic approaches, injury modelling, translational research or other experiments, a dependable animal model is indispensable for experiment validity (Song & Pan, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Numerous researchers have advocated for the use of pigs as an ideal animal model due to their anatomical similarities with humans. Pigs have emerged as a prominent species for fundamental and preclinical research (Netzley & Pelled, 2023; Song & Pan, 2019; Swindle et al., 2012). Of particular interest is the porcine cornea, which closely resembles the human cornea in terms of thickness, topography and refractive stability (Jay et al., 2008; Kampmeier et al., 2000).…”

Section: Introductionmentioning

confidence: 99%

Histology, histochemistry and ultrastructure of cornea of domestic pigs (Sus scrofa domesticus)

Barhaiya,

Kumar

2024

Anat Histol Embryol

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A comprehensive light and ultrastructural examination of the cornea in Domestic Pigs (Sus scrofa domesticus) revealed four distinct layers: the anterior epithelium, corneal stroma, Descemet's membrane and endothelium. Although Bowman's layer was not distinctly identified through histology, histochemical analysis indicated the presence of a rudimentary Bowman's layer, possibly vestigial from evolution. Scanning electron microscopy of the outer corneal surface unveiled two cell types, characterized by micro‐projections, with light cells exhibiting shorter, thicker projections compared to dark cells. Examination of the inner surface via scanning electron microscopy demonstrated an endothelial layer devoid of cilia and microvilli, yet faint round to oval elevations were observed, potentially representing cell nuclei. Transmission electron microscopy unveiled that basal cells of the anterior epithelium closely adhered to the basement membrane, featuring half desmosomes along the basal surface. These basal cells extensively interconnected through interdigitations and a few desmosomes. The superficial cell layer consisted of a few rows of closely attached flat cells, forming a leak‐proof layer with zona occludens. The outermost cells of this layer displayed fine projections to enhance the surface area, facilitating tear film distribution. At lower magnification, Transmission electron microscopy of the corneal stroma revealed alternating light and dark bands, with light bands representing transverse sections of collagen fibril lamellae and dark bands corresponding to longitudinal or oblique sections. Spindle‐shaped keratocytes (fibroblasts) were identified as the primary stromal cells, intermingled between the lamellae, and featured long processes in close contact with neighbouring keratocytes. Overall, the histomorphology of the pig cornea resembles that of the human cornea except indistinct Bowman's membrane. This detailed understanding of the normal corneal structure in pigs hold great significance for biomedical research, providing a valuable reference for studies involving this animal model.

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“…The platform uses discarded whole eyes from local abattoirs to create corneal grafts or scaffolds that can be used for various purposes, namely, in vitro and in vivo models that can ultimately generate patient-specific keratoprostheses, and provide a platform for pharmacological testing and cell and gene therapies that are poised to support bioartificial organ development ( Kong and Mi, 2016 ; Ahearne et al, 2020a ; Wang Xe et al, 2023 ). Our data extensively outlines ways to effectively generate scaffolds that preserve the appreciable levels of ocular transparency, transmittance, and ECM components for applicability as native ovine grafts ( Niu et al, 2019 ), which can be genetically modified to reduce rejection and retrovirus transmission in the recipient ( Song and Pan, 2019 ). Comparable characterizations are carried out for scaffolds created from decellularization, which produces extracellular matrix-based substrates with attributes similar to the native xenografts for driving corneal regeneration ( Wilson et al, 2016 ; Polisetti et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

A scalable corneal xenograft platform: simultaneous opportunities for tissue engineering and circular economic sustainability by repurposing slaughterhouse waste

Wang

Shakeel

Salih

et al. 2023

Front. Bioeng. Biotechnol.

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Introduction: Corneal disease is a leading cause of blindness globally that stems from various etiologies. High-throughput platforms that can generate substantial quantities of corneal grafts will be invaluable in addressing the existing global demand for keratoplasty. Slaughterhouses generate substantial quantities of underutilized biological waste that can be repurposed to reduce current environmentally unfriendly practices. Such efforts to support sustainability can simultaneously drive the development of bioartificial keratoprostheses.Methods: Scores of discarded eyes from the prominent Arabian sheep breeds in our surrounding region of the United Arab Emirates (UAE) were repurposed to generate native and acellular corneal keratoprostheses. Acellular corneal scaffolds were created using a whole-eye immersion/agitation-based decellularization technique with a widely available, eco-friendly, and inexpensive 4% zwitterionic biosurfactant solution (Ecover, Malle, Belgium). Conventional approaches like DNA quantification, ECM fibril organization, scaffold dimensions, ocular transparency and transmittance, surface tension measurements, and Fourier-transform infrared (FTIR) spectroscopy were used to examine corneal scaffold composition.Results: Using this high-throughput system, we effectively removed over 95% of the native DNA from native corneas while retaining the innate microarchitecture that supported substantial light transmission (over 70%) after reversing opacity, a well-established hallmark of decellularization and long-term native corneal storage, with glycerol. FTIR data revealed the absence of spectral peaks in the frequency range 2849 cm−1 to 3075 cm−1, indicating the effective removal of the residual biosurfactant post-decellularization. Surface tension studies confirmed the FTIR data by capturing the surfactant’s progressive and effectual removal through tension measurements ranging from approximately 35 mN/m for the 4% decellularizing agent to 70 mN/m for elutes highlighting the effective removal of the detergent.Discussion: To our knowledge, this is the first dataset to be generated outlining a platform that can produce dozens of ovine acellular corneal scaffolds that effectively preserve ocular transparency, transmittance, and ECM components using an eco-friendly surfactant. Analogously, decellularization technologies can support corneal regeneration with attributes comparable to native xenografts. Thus, this study presents a simplified, inexpensive, and scalable high-throughput corneal xenograft platform to support tissue engineering, regenerative medicine, and circular economic sustainability.

show abstract

Reducing porcine corneal graft rejection, with an emphasis on porcine endogenous retrovirus transmission safety: a review

Cited by 6 publications

References 74 publications

Cardiac Xenotransplantation

Cardiac Xenotransplantation

Histology, histochemistry and ultrastructure of cornea of domestic pigs (Sus scrofa domesticus)

A scalable corneal xenograft platform: simultaneous opportunities for tissue engineering and circular economic sustainability by repurposing slaughterhouse waste

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