The feasibility and efficacy of preparing porcine Descemet’s membrane endothelial keratoplasty (<scp>DMEK</scp>) grafts by two techniques: An ex‐vivo investigation for future xeno‐<scp>DMEK</scp>

Liu, Yang; Zhang, Jing; Zhang, Yingnan; Yin, Mingyang; Miao, Sen; Liang, Qingfeng; Pan, Zhiqiang

doi:10.1111/xen.12407

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…Preparing porcine whole DMEK lamellar tissues is challenging due to the strong adhesivity between stroma and DM, as well as to the elastic properties of the donor grafts (obtained from young animals, aged 6–8 months), which increased the difficulty of the surgical manipulation. 47 Liu and colleagues 48 successfully achieved DMEK lamellar preparations from porcine corneas employing older (10–12 months) animal tissues but were unsuccessful with younger ones. In order to overcome this age-related technical challenge, we developed a method of preparing what we called porcine lamellar fragments consisting of DM and EC, which allowed for examination and comparison with human DMEK lamellar tissues.…”

Section: Discussionmentioning

confidence: 99%

Porcine Cornea Storage Ex Vivo Model as an Alternative to Human Donor Tissues for Investigations of Endothelial Layer Preservation

Rodella

Bosio

Ferrari

et al. 2023

Trans. Vis. Sci. Tech.

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Purpose Due to the growing shortage of human corneas for research, we developed a porcine cornea storage model with qualitative features comparable to human tissues. Methods We established a decontamination procedure for porcine eye bulbs to ensure corneal storage at 31°C to 35°C for up to 28 days without contamination. We compared human and porcine corneas under hypothermic (2–8°C) or culture (31–35°C) conditions for central corneal thickness (CCT), corneal transparency, endothelial morphology, endothelial cell density (ECD), and a novel method to quantify whole endothelial mortality. We also examined portions of lamellar tissues consisting of Descemet's membrane and endothelial cells under the microscope after Alizarin red staining. Results Our decontamination procedure reduced corneal contamination from 94% (control corneas without decontamination) to 18% after 28 days of storage at 31°C to 35°C. ECD, CCT, transparency, and morphology were significantly higher in porcine corneas than in human corneas at day 0. Nevertheless, the qualitative parameters of porcine and human corneas showed comparable trends under both investigated storage conditions for up to 14 days. Conclusions The presented corneal storage model provides a reliable alternative to human tissues for preliminary corneal investigations. Translational Relevance The porcine cornea storage model can be used to investigate the efficacy and safety of new media, substances, or storage conditions. Furthermore, the method developed to assess the percentage of endothelial mortality is tissue conservative and can be used in eye banks to monitor endothelial mortality during storage of tissues intended for transplantation.

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Section: Discussionmentioning

confidence: 99%

Porcine Cornea Storage Ex Vivo Model as an Alternative to Human Donor Tissues for Investigations of Endothelial Layer Preservation

Rodella

Bosio

Ferrari

et al. 2023

Trans. Vis. Sci. Tech.

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“…All xenograft recipients developed a retrocorneal membrane, with infiltration by CD3+ T cells at the corneal stroma, and manifested increased IL‐6 expression six months after transplantation . In order to prepare the porcine descemet membrane endothelial keratoplasty (DMEK) grafts, Zhiqiang Pan applied a mechanical stripping and liquid bubble technique, resulting in the conclusion that xeno‐DMEK could be a promising approach for pig cornea transplantation . This study also showed that there was no PERV transmission from Wuzhishan minipigs to rhesus monkey recipients .…”

Section: Pig‐to‐nonhuman Primate Xenotransplantation In Chinamentioning

confidence: 92%

Xenotransplantation in China: Present status

Wang

Lei

Liang³

et al. 2019

Xenotransplantation

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The main obstacle to organ transplantation is the shortage of organs from deceased individuals. Especially in China, the ratio of patients on the waiting list versus the transplant recipients is 30:1. Therefore, there is an urgent need for organ donors. Genetically modified pig organs have proved to be a new source for xenotransplantation, and Chinese scientists have made considerable progress in this area during recent years. In this paper, we review four important aspects of the xenotransplantation field in China. First, a large variety of genetically modified pigs have been generated by Chinese scientists: all these genetically modified pigs and the purpose of these modifications will be summarized. Second, the preclinical research in pig‐to‐nonhuman primate xenotransplantation is outlined. The survival time and major biochemical parameters for the xenografts are summarized. Third, regarding the bench‐to‐bed approach, more suitable organs have been developed for xenotransplantation in humans, and in particular, pig islet transplantation into diabetic patients as well as pig‐to‐human cornea and skin transplantation. Fourth, we briefly address the regulations and prospects for recruiting xenotransplantation experts in China. Based on recent progress, we anticipate that genetically modified pigs will offer suitable organs for the treatment of end‐stage organ diseases in humans in the near future. Given the recent influx of world‐renowned scientists in xenotransplantation to China, our country will definitely become one of the major centers of xenotransplantation research and development in the world.

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“…Moreover, EK may need a weaker immunosuppressive regimen and shows less risk of xenozoonosis than PKP since there are fewer porcine cells in the posterior lamellar graft. Porcine corneas, unlike humans, have strong Descemet membrane-stroma adhesion ( Liu et al, 2018 ). Therefore, a donor graft preparation for Descemet membrane endothelial keratoplasty (DMEK) is challenging.…”

Section: Preclinical Efficacy Data Of Porcine Corneal Xenotransplantamentioning

confidence: 99%

“…Hence, pig-to-NHP DMEK has not been reported yet. Recently, a study on how to produce DMEK graft using porcine cornea has been published ( Liu et al, 2018 ). Regarding Descemet stripping automated endothelial keratoplasty (DSAEK), there was one study reporting long-term survivals of the porcine grafts in NHPs with CS ( Liu et al, 2019 ).…”

Section: Preclinical Efficacy Data Of Porcine Corneal Xenotransplantamentioning

confidence: 99%

Corneal xenotransplantation: Where are we standing?

Yoon¹,

Choi²,

Kim

2021

Progress in Retinal and Eye Research

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The search for alternatives to allotransplants is driven by the shortage of corneal donors and is demanding because of the limitations of the alternatives. Indeed, current progress in genetically engineered (GE) pigs, the introduction of gene-editing technology by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, and advanced immunosuppressants have made xenotransplantation a possible option for a human trial. Porcine corneal xenotransplantation is considered applicable because the eye is regarded as an immune-privileged site. Furthermore, recent non-human primate studies have shown long-term survival of porcine xenotransplants in keratoplasty. Herein, corneal immune privilege is briefly introduced, and xenogeneic reactions are compared with allogeneic reactions in corneal transplantation. This review describes the current knowledge on special issues of xenotransplantation, xenogeneic rejection mechanisms, current immunosuppressive regimens of corneal xenotransplantation, preclinical efficacy and safety data of corneal xenotransplantation, and updates of the regulatory framework to conduct a clinical trial on corneal xenotransplantation. We also discuss barriers that might prevent xenotransplantation from becoming common practice, such as ethical dilemmas, public concerns on xenotransplantation, and the possible risk of xenozoonosis. Given that the legal definition of decellularized porcine cornea (DPC) lies somewhere between a medical device and a xenotransplant, the preclinical efficacy and clinical trial data using DPC are included. The review finally provides perspectives on the current standpoint of corneal xenotransplantation in the fields of regenerative medicine.

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The feasibility and efficacy of preparing porcine Descemet’s membrane endothelial keratoplasty (DMEK) grafts by two techniques: An ex‐vivo investigation for future xeno‐DMEK

Cited by 8 publications

References 38 publications

Porcine Cornea Storage Ex Vivo Model as an Alternative to Human Donor Tissues for Investigations of Endothelial Layer Preservation

Porcine Cornea Storage Ex Vivo Model as an Alternative to Human Donor Tissues for Investigations of Endothelial Layer Preservation

Xenotransplantation in China: Present status

Corneal xenotransplantation: Where are we standing?

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