1.Current Status of Solid Organ Xenotransplantation.
The Journal of the Korean Society for Transplantation 2016;30(2):69-76
Solid organ xenotransplantation using transgenic pig organs is proposed as an alternative method for allo-transplantation. To accomplish this, immunologic and non-immunologic barriers for xenotransplantation should be overcome, and experiments on pigs to non-human primates (NHP) are now ongoing for clinical application. Before the clinical experiment, public consensus about ethical decisions must be considered. The results of NHP experiments on solid organ xenotransplantation are improving, and it is expected that xeno-solid organs can be used as new organs for human patients in the future.
Consensus
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Humans
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Methods
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Primates
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Swine
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Transplantation, Heterologous*
3.Key issues related to clinical trials of xenotransplantation.
Hao XU ; Xuan ZHANG ; Ke Feng DOU
Chinese Journal of Surgery 2022;60(10):888-893
The development of xenotransplantation is expected to alleviate the supply and demand gap of donors' organs. Currently,gene-edited pigs are considered as ideal organ donor source for clinical xenotransplantation. Driven by relevant technologies,substantial progress have been achieved in preclinical studies of xenotransplantation,which creates good conditions for the opening of early clinical trials. Especially in recent two years,the foreign clinical research in this field has made a breakthrough. Here,the progress in xenotransplantation of clinical trials is briefly reviewed home and abroad,the key issues in clinical trials of xenotransplantation are discussed from the perspectives of gene editing of donor pigs,principles of whole-course management of subjects,ethics and social psychology issue. It is believed that under the background of multidisciplinary cross-fusion,xenotransplantation will be gradually transferred to clinical application in the future,and better benefit human beings.
Animals
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Humans
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Swine
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Tissue Donors
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Transplantation, Heterologous
5.The Study of Characteristics of Acellular Porcine Cornea Using Freezing-Thawing-Centrifugation.
Seok Hyun LEE ; Yeoun Sook CHUN ; Jae Chan KIM
Journal of the Korean Ophthalmological Society 2011;52(1):86-92
PURPOSE: To develop a new decellularization technique of porcine cornea using freezing-thawing-centrifugation (FTC) and to examine the characteristics of acellular porcine cornea (APC) for xenograft material. METHODS: Two-hundred micrometer thickness porcine corneas were decellularized with DNase/RNase, followed by 3 freezing-thawing-centrifugations (FTC, group 1), lyophilized FTC-APC (group 2), and chemical enzyme treated APC (CE-APC, group 3). Histologic evaluation to examine cells and collagen matrix, comparison of transparency, and cultivation to determine the viability of stromal cells was performed in fresh porcine cornea and 3 experimental groups. RESULTS: Decellularization occurred successfully in all experimental groups. Decellularization was confirmed by H&E staining and cultivation. Transparency of group 1 was similar to the normal porcine cornea but transparency of group 2 and group 3 was decreased. Collagen fibers of CE-APC (group 3) were not as well arrayed as FTC-APC (group 2). CONCLUSIONS: Acellularity of porcine cornea was successfully achieved by the FTC method with preservation of the cornea stroma. Novel decellularized porcine cornea can be considered as xenogeneic material for corneal transplantation.
Collagen
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Cornea
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Corneal Transplantation
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Stromal Cells
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Transplantation, Heterologous
6.Bottleneck and development trend of bone xenograft for the treatment of bone defect.
Bao-liang LI ; Lei LIU ; Wen-bo ZHAO ; Fu-jun LUAN ; Qin LI
China Journal of Orthopaedics and Traumatology 2015;28(12):1166-1170
Bone xenograft bone for the treatment of bone defect is one of the current research focus, which has advantages of extensive sources, low cost, simple preparation method. While the process of single bone xenograft bone in repairing bone defect is very long, and the clinical outcome is not satisfactory. The main problems focus on formation of bone and vascularization. Reconstituted bone xenograft combined with cells and xenogenic bone material could promote vascularization and bone fusion in vivo, thus achieve a clinical effect of autogenous bone in repairing bone defect.
Bone Transplantation
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methods
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Bone and Bones
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blood supply
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Humans
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Transplantation, Heterologous
7.Experimental study of acellular xenogenic dermal matrix and allogeneic sclera as wrapping materials for hydroxy apatite implantation.
Zhao-yan HE ; Yan-nian HUI ; Quan-hong HAN ; Lin WANG ; Zi-feng ZHANG ; Jing HAN
Chinese Journal of Plastic Surgery 2006;22(3):216-220
OBJECTIVETo observe the experimental results and histopathological changes of acellular xenogenic dermal matrix (X-ADM) and allogeneic sclera used as wrapping materials of hydroxy apatite (HA) ocular implants in New Zealand white rabbits.
METHODSTwenty-four rabbits received unilateral eye enucleating and the sockets were implanted with HA spherical implants wrapped with either acellular xenogenic dermal matrix or allogeneic sclera at random. The rabbits were examined for inflammation and implant exposure and sacrificed at 1, 2, 4, 6, 8 and 12 weeks after implantation. The sockets with the grafts were exenterated and the specimens were assessed histopathologically and ultrastructurally with light or transmission electron microscopy for the changes in inflammation reaction and vascularization.
RESULTSCompared to allogeneic sclera at the same stage of implantation, acellular xenogenic dermal matrix demonstrated more active and earlier growth of fibroblasts and new vessels with abundant collagen deposition. There were few inflammatory cells and no rejection was found.
CONCLUSIONThis experiment showed that the acellular xenogenic dermal matrix, with fast neovascularization and low immunity, can be an ideal material of ocular implant and a good substitute for allogeneic sclera.
Animals ; Dermis ; transplantation ; Eye, Artificial ; Female ; Hydroxyapatites ; Male ; Rabbits ; Sclera ; transplantation ; Swine ; Transplantation, Heterologous ; Transplantation, Homologous
8.Induction of Acute Cyclosporine Nephrotoxicity in Pig.
Jin Young KIM ; Sun Woo LIM ; Kyung Ok AHN ; Hyun Kuk SONG ; Jung Yeon GHEE ; Byung Ha CHUNG ; Yong Soo KIM ; Byung Kee BANG ; Chul Woo YANG
The Journal of the Korean Society for Transplantation 2007;21(1):58-62
PURPOSE: Pigs are promising donor species for xenotransplantation. This study was performed to examine acute cyclosporine (CsA) nephrotoxicity in a pig model. METHODS: Adult pigs were treated daily for 1 week with vehicle (VH), or 7.5 mg/kg (CsA7.5), 15 mg/kg (CsA15), and 30 mg/kg (CsA30) CsA. The renal function, electrolyte levels, whole- blood CsA levels, and histopathological results (vacuolization and tubulointerstitial fibrosis) were compared among the different treatment groups. RESULTS: After 1 week of treatment, it was found that CsA induced characteristic lesions that were remarkably similar to those of chronic CsA nephropathy in humans. Compared with the results obtained for the VH group, CsA reduced renal function and yielded poor histopathological results. With an increase in the CsA concentration, the renal function and histological parameters worsened in a dose-dependent manner. CONCLUSION: The study showed that CsA dose-dependently induced renal injury in a pig model. These results provide basic data to estimate or prevent the adverse renal effects of immunosuppressants during porcine xenotransplantation in the future.
Adult
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Cyclosporine*
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Humans
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Immunosuppressive Agents
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Swine
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Tissue Donors
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Transplantation, Heterologous
9.Serum Lmmunoglobulin G and M Level after Xenograft Valve or Valved Conduit Implantation.
Jae Gun KWAK ; Jae Suk YOO ; Sun Hee YOON ; Woong Han KIM ; Kyung Hwan KIM ; Yong Jin KIM
The Korean Journal of Thoracic and Cardiovascular Surgery 2008;41(2):223-228
BACKGROUND: The aim of this study is to confirm that peripheral blood sampling for measuring of serum immunoglobulin can predict immunological changes after xenograft implantation. MATERIAL AND METHOD: Between March 2006 and January 2007, 19 patients were enrolled (10 xenograft implantation group, 9 control group). Through 3 peripheral blood samples, we measured changes in serum immunoglobulin G and M levels preoperatively, and 2 and 10 days postoperatively. RESULT: In both groups, serum immunoglobulin levels showed similar changes-they decreased 2 days postoperatively, then increased up to the baseline levels 10 days postoperatively. However, this postoperative change of immunoglobulin G and M was not significantly different in absolute value or pattern between the 2 groups (Ig G; p-value=0.393, Ig M; p-value=0.193). CONCLUSION: We could not predict immunological changes after xenograft implantation by measuring serum immunoglobulin levels by simple blood sampling. Direct checking of alpha-Galactose antibody may confirm an immunological reaction after xenograft implantation.
Heart Valve Prosthesis
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Humans
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Immunoglobulin G
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Immunoglobulins
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Transplantation, Heterologous
10.Holstein-Friesian RBC as human blood substitute.
Li-Ping CHEN ; Su-Bo LI ; Xue ZHANG ; Feng GONG ; Hong-Wei GAO ; Hua XU
Journal of Experimental Hematology 2014;22(4):1099-1102
α-Gal, the main xenotransplantation antigen, can lead to hyperacute rejection (HAR) in xenotransplantation. This study was purposed to investigate the effect of recombinant α-galactosidase (α-Gal antigen) on the Holstein-Friesian(H-F) red blood cells (RBC). The enzymelysis method was used to digest the α-Gal antigen on H-F RBC; the saline and anti-human globulin methods were used to perform the agglutination test of H-F RBC and human plasma; the flow cytometry was used to detect the α-Gal antigen on surface of H-F RBC, fluorescence intensity of FITC-IB4 and FITC-IgG labeled RBC. The results indicated that the saline and anti-human globulin method showed α-galactosidase-treated H-F RBC fail to agglutinate with human pooled plasma; the flow cytometry showed the fluorescence intensity of FITC-IB4 and FITC-IgG labeled RBC decrease 99.0% and 87.8%, respectively. It is concluded that the novel α-galactosidase can be used to cleared the α-Gal antigen on the surface of H-F RBC and α-galactosidase-treated H-F RBC may be considered as human blood substitute.
Animals
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Blood Substitutes
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Cattle
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Erythrocytes
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immunology
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Female
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Humans
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Transplantation, Heterologous