Xenotransplantation in Sweden.
Year: 1999
Type: article
Abstract: Several Swedish research groups are working actively in the field of xenotransplantation. Recently, these efforts have resulted in two clinical pilot trials: 10 diabetic patients have been transplanted with porcine pancreatic islets, and two patients have had pig kidneys connected to their blood circulation and perfused extracorporeally. Transplantation of porcine islets Transplantation of isolated pancreatic islets offers a simple and safe method to provide the diabetic patient with insulin-producing tissue. If such transplantation is to be widely applied, the supply of human pancreases will not suffice. Transplantation of pig islets could then serve as an alternative. Porcine insulin differs from human insulin only in regard to one amino acid, and glucose homoeostasis and the regulation of insulin secretion are similar in pig and man. Furthermore, porcine insulin has been used for decades to treat diabetic patients. Since the transplanted islets will become vascularized by host vessels, hyperacute rejection should not occur. Fetal porcine islets can be prepared in large quantities by tissue digestion and culture. After transplantation, the fetal cells mature and differentiate into insulin-producing cells. Microbiological screening revealed no infectious agents in the material, and, when the material was injected intraportally in dogs, no adverse effects were noted. On the basis of the above findings, a clinical pilot trial was conducted in the years 1990-1993 in 10 diabetic renal transplant patients. All patients were given immunsuppressive treatment because of their renal transplant (1). Eight patients who had previously undergone kidney transplantation had the porcine islets injected into the portal vein. Four of the patients excreted small amounts of porcine C-peptide for 100-400 days after transplantation, indicating porcine insulin production. In two patients, the islets were placed under the capsule of their renal graft just after the graft had been revascularized. In one of the patients, a kidney biopsy specimen taken three weeks after transplantation revealed morphologically intact epithelial cells under the kidney capsule. These cells stained positively for insulin and glucagon. Ultrastructural and immunocytochemical features were typical of pancreatic islet cells; the appearance of the cells indicated that they were viable (2). All patients had preformed xenoantibodies against the Gal 1,3Gal, an antigen epitope present on porcine but not on human cells. After transplantation there was a pronounced increase in the antibody titres (3). The finding that the porcine islets did not function at all in some patients, and only for a limited time in the others, probably indicates rejection. The role of the xenoantibodies in this process remains obscure. The patients derived no clinical benefit from the transplantation in that their insulin requirements remained unaffected. A larger and longer-lasting insulin production will be required to accomplish a clinical benefit. Recently, we have isolated adult pig islets which provide immediate function. When such islets were transplanted into unmodified rats, rejection occurred in 4-5 days. However, when the rats were treated with novel immunosuppressive drug regimens, rejection was prevented for several weeks (4). These encouraging findings will provide the basis for further trials with pig-to-human islet transplantation. Extracorporeal (ex vivo) perfusion of pig kidneys in two patients Removal of the preformed xenoantibodies by immunoadsorption, or plasmapheresis should facilitate xenograft survival. In order to test this concept, we performed a clinical trial in 1995 where pig kidneys were extracorporeally connected to the blood circulation of two volunteer dialysis patients. The procedure was similar to an ordinary dialysis, except that the dialysis filter was replaced by a pig kidney. Prior to the procedure, the patients underwent plasmapheresis with a subsequent reduction in xenoantibody titres. …
Source: Europe PMC (PubMed Central)
Authors: C G Groth, M E Breimer
Institution: Karolinska Institutet
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W182248765