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      Therapeutic Promise of Embryonic Kidney Transplantation

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          One novel solution to the shortage of human kidneys available for transplantation envisions ‘growing’ new kidneys in situ via xenotransplantation of renal anlagen. We and others have shown that developing metanephroi transplanted into animal hosts undergo differentiation and growth, become vascularized by blood vessels of host origin and exhibit excretory function. Metanephroi can be stored for up to 3 days in vitro prior to transplantation with no impairment in growth or function post-implantation. Metanephroi can be transplanted across both concordant (rat to mouse) and discordant/highly disparate (pig to rodent) xenogeneic barriers. Here we review studies exploring the potential therapeutic use of embryonic kidney transplantation.

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          Most cited references 6

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          Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs.

          Galactose-alpha1,3-galactose (alpha1,3Gal) is the major xenoantigen causing hyperacute rejection in pig-to-human xenotransplantation. Disruption of the gene encoding pig alpha1,3-galactosyltransferase (alpha1,3GT) by homologous recombination is a means to completely remove the alpha1,3Gal epitopes from xenografts. Here we report the disruption of one allele of the pig alpha1,3GT gene in both male and female porcine primary fetal fibroblasts. Targeting was confirmed in 17 colonies by Southern blot analysis, and 7 of them were used for nuclear transfer. Using cells from one colony, we produced six cloned female piglets, of which five were of normal weight and apparently healthy. Southern blot analysis confirmed that these five piglets contain one disrupted pig alpha1,3GT allele.
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            Transplantation of porcine fetal pancreas to diabetic patients.

            Transplantation of fetal porcine islet-like cell clusters (ICC) reverses diabetes in experimental animals. We have now transplanted porcine ICC to ten insulin-dependent diabetic kidney-transplant patients. All patients received standard immunosuppression and, at ICC transplantation, antithymocyte globulin or 15-deoxyspergualin. ICC were injected intraportally or placed under the kidney capsule of the renal graft. Four patients excreted small amounts of porcine C-peptide in urine for 200-400 days. In one renal-graft biopsy specimen, morphologically intact epithelial cells stained positively for insulin and glucagon in the subcapsular space. We conclude that porcine pancreatic endocrine tissue can survive in the human body.
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              A simple procedure for the isolation of rat kidney lysosomes.

              A procedure for the isolation of highly purified lysosomes from normal rat kidney is described. The method depends on the swelling of mitochondria when the postnuclear supernatant fraction is incubated with 2 mM Ca2+. The lysosomes can then be separated from the swollen mitochondria by Percoll density gradient centrifugation. The lysosomal fraction obtained by our method was enriched more than 30-fold in terms of marker enzymes with a yield of about 11%. Electron microscopic examination and the measurement of the activities of marker enzymes for various subcellular organelles indicated that our lysosomal preparation was essentially free from contamination by other organelles. We believe that this procedure for isolating kidney lysosome will be useful in the study of the mechanisms of specific modification, processing and catabolism of proteins.

                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                February 2003
                17 November 2004
                : 93
                : 2
                : e58-e62
                George M. O’Brien Kidney and Urological Disease Center, Renal Division, Departments of Medicine, and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Mo., USA
                68516 Nephron Exp Nephrol 2003;93:e58–e62
                © 2003 S. Karger AG, Basel

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                Page count
                Figures: 2, Tables: 1, References: 21, Pages: 1
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/68516


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