The effect of lyophilization on graft acceptance in experimental xenotransplantation using porcine cornea.
ABSTRACT The immunogenicity of lyophilized porcine cornea is unknown. The purpose of this study was to examine the possibility of using lyophilized porcine cornea as a substrate for ocular surface reconstruction. A porcine cornea stromal button was freeze-dried and vacuum-packed. Lyophilized and fresh porcine corneas were examined histologically, and then implanted into intrastromal pockets in live rat corneas. Cytokine concentrations in plasma and protein extracts from the corneal buttons of rats were measured using the fluorokine multianalyte profiling assay, and histologic examination was performed. Immunoreactivity to the alpha-gal epitope was not found in lyophilized porcine corneas, whereas it was found in several keratocytes in fresh porcine corneas. The median survival time of rat corneas receiving lyophilized porcine transplants was 28.0 days, significantly longer than the 14.0-day survival of rat corneas that received fresh porcine transplants (P < 0.05). CD45RO(+) and CD68(+) cells were observed in rejected corneas, and interleukin-2 and interferon-gamma were elevated in rat plasma and corneal tissue. The lyophilized porcine corneal stroma, which is devoid of alpha-gal epitope, is less antigenic, and may be a useful biomaterial for ocular surface reconstruction and corneal collagen supplementation.
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ABSTRACT: The framework of differential algebra, especially Ritt’s algorithm, has turned out to be a useful tool when analyzing the identifiability of certain nonlinear continuous-time model structures. This framework provides conceptually interesting means to analyze complex nonlinear model structures via the much simpler linear regression models. One difficulty when working with continuous-time signals is dealing with white noise in nonlinear systems. In this paper, difference algebraic techniques, which mimic the differential-algebraic techniques, are presented. Besides making it possible to analyze discrete-time model structures, this opens up the possibility of dealing with noise. Unfortunately, the corresponding discrete-time identifiability results are not as conclusive as in continuous time. In addition, an alternative elimination scheme to Ritt’s algorithm will be formalized and the resulting algorithm is analyzed when applied to a special form of the nfir model structure.Automatica 01/2011; 47(9):1896-1904. · 2.92 Impact Factor
Article: Xenocorneal transplantation.[Show abstract] [Hide abstract]
ABSTRACT: Donor shortage in corneal transplantation is a significant problem in Asian countries and is an emerging issue worldwide. This review will discuss current knowledge of the pathogenesis of the rejection mechanism, recent advances in xenocorneal transplantation, and feasibility of porcine xenocorneal graft. α-Gal epitopes which are expressed on the porcine cornea, however less than in other vascularized organs. A small animal model provided evidence of complement-mediated or antibody-mediated rejection in porcine xenocorneal transplantation. Recent progress in genetic engineering of the pig or biomedical engineering for removal of the α-Gal epitope appears to have resulted in reduction of antibody-mediated rejection. Porcine corneal xenograft is not rejected hyperacutely in all animal models. T cells predominantly mediate xenocorneal rejection through various animal models. Survival of lamellar fresh porcine grafts is longer than that of full-thickness fresh porcine grafts. Decellularized porcine grafts also demonstrate significantly longer survival than fresh grafts do. Recent studies have documented the potential of the porcine corneal graft as a substitute for use in human allograft and have highlighted the mechanisms of rejection of xenocorneal transplantation. Antibody-mediated or complement-mediated xenogeneic rejection should be further explored in a large animal model.Current opinion in organ transplantation 04/2011; 16(2):231-6. · 3.27 Impact Factor
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ABSTRACT: BACKGROUND: To establish the consensus about the conditions for undertaking clinical trials in xenocorneal transplantation in Korea, specific issues regarding the xenocorneal transplantation on ethical and regulatory aspects are addressed, and the guidelines to conduct clinical trial of the xenocorneal transplantation are proposed. METHOD AND RESULTS: Chapter 1 reviews the key ethical requirements and progress of a Korean regulatory framework for clinical trials of xenocorneal transplantation. Chapters 2-7 provide recommendations on source pigs, quality control of porcine corneal procurement, preclinical efficacy required to justify a clinical trial, strategies to prevent transmission of porcine endogenous retrovirus (PERV), patient selection for clinical trials, and informed consent in xenocorneal transplantation using either cellularized or decellularized porcine graft, which are essentially based on the International Xenotransplantation Association (IXA) islet xenotransplantation consensus statement. The consensus statement of the inclusion criteria for the patients' selection has been made by the executive board members in Korean External Eye Disease Society. CONCLUSIONS: This consensus statement will be a good initiative for Korean Food and Drug Administration to discuss final regulatory guidelines in conducting clinical trials of xenocorneal transplantation in Korea and for International Xenotransplantation Association to develop International Consensus Standards of Xenocorneal Transplantation.Xenotransplantation 05/2013; · 2.57 Impact Factor