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Abstract
Islet xenotransplantation is one prospective treatment to bridge the gap between available human cells and needs of patients with diabetes. Pig represents an ideal candidate for obtaining such available cells. However, potential clinical application of pig islet still faces obstacles including inadequate yield of high-quality functional islets and xenorejection of the transplants. Adequate amounts of available islets can be obtained by selection of a suitable pathogen-free source herd and the development of isolation and purification method. Several studies demonstrated the feasibility of successful preclinical pig-islet xenotransplantation and provided insights and possible mechanisms of xenogeneic immune recognition and rejection. Particularly promising is the achievement of long-term insulin independence in diabetic models by means of distinct islet products and novel immunotherapeutic strategies. Nonetheless, further efforts are needed to obtain much more safety and efficacy data to translate these findings into clinic.
Highlights
Diabetes is one of the most dangerous threats to human health
Encouraging findings have been obtained in pig-to-primate islet xenotransplantation [9,10,11], the potential clinical application of pig islet still faces two major challenges: inadequate supply of islet cells with high-quality and xenorejection
All the data indicate that natural anti-Gal antibodies do not appear to play a major role in the immune rejection of adult pig islets (APIs) in diabetic non-human primates (NHPs)
Summary
Diabetes is one of the most dangerous threats to human health. pancreatic islet transplantation has gradually showed satisfactory and prospective application in the treatment of type 1 diabetes mellitus (T1DM) [1]. Published study reported an extremely high APIs yield, up to 800,000 IEQ per pancreas after purification [37] The achievements make it possible to perform single pig donor clinical xenogeneic transplantation. ISOLATION AND PREPARATION OF PORCINE ISLETS Islet-like cell clusters and NPIs can be obtained by simple enzymatic digestion and subsequent pre-transplantation culture due to relative lack of exocrine tissues and concomitant relative abundance of endocrine tissues [23, 24, 46]. Factors including quality status of donor pancreas, blood exsanguinations, warm ischemia time (WIT), perfusate, types of digestive enzyme, and isolation/purification process will affect the islet yield and function [47,48,49]. Islet recovery decreased dramatically after prolonged culture (7– 14 days), the APIs displayed shorter time-to-normoglycemia and reversed hyperglycemia in all recipients
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