Canine Pancreatic Islet Transplantation: A Comparison of Two Isolation Techniques

Abstract

A new method (type B) for isolation of canine islets was developed, utilizing intraductal collagenase perfusion, stationary digestion, filtration and tissue separation by means of a dextran density gradient. The results of this technique were compared with those of a previously established method (type A). Islets were autotransplanted either via the splenic or the portal vein. Lasting normoglycemia was obtained in 5/8 intrasplenic type B transplants (63%), 6/8 intrahepatic type B transplants (75%), 5/6 intrasplenic type A transplants (83%) and 0/3 intrahepatic type A transplants. No difference was found in metabolic parameters 2 weeks after successful transplantation following type A or B islet isolation. Islet yield was higher with type A and purification better with type B isolation. Both techniques are relatively simple and inexpensive. Because of its higher purification rate and the success of intrahepatic islet transplantation method B has replaced method A as the routine procedure in our laboratory.

The Spleen as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells

“…Historically, intrasplenic islet transplantation has been performed since the late 1970s, when several trials of intrasplenic islet autotransplantation into pancreatectomized dogs demonstrated recovery of endocrine function [ 89 , 90 , 91 , 92 ]. This model has been used to assess transplantation efficacy [ 89 , 90 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 ], and also to assess the transplantation of cold-preserved or cryopreserved islets [ 103 , 104 , 105 , 106 ] and the toxicity of immunosuppressants [ 95 , 107 , 108 , 109 , 110 ]. Other animals, including pigs [ 111 ] and monkeys [ 112 , 113 , 114 ], have also been used for islet autotransplantation and have shown acceptable outcomes.…”

“…Using fetal porcine allotransplantation and murine transplantation models, Stokes et al showed a higher transplantation efficacy for the spleen compared with the liver, although the kidney was better [ 129 , 130 ]. Many other studies have reported superiority of the spleen compared with the liver [ 100 , 111 ] or omental pouch [ 56 , 131 ], although some groups have reported opposite results [ 97 , 98 , 99 ] ( Table 3 ).…”

Spleen, as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells

“…Historically, intrasplenic islet transplantation has been performed since the late 1970s, when a number of trials looking at intrasplenic islet autotransplantation into pancreatomized dogs demonstrated that this method could result in the recovery of endocrinal function [87][88][89][90]. This model has been used not only for the assessment of transplantation efficacy [87,88,[90][91][92][93][94][95][96][97][98][99][100], but also for the assessment of the transplantation of cold or cryopreserved islets [101][102][103][104] and the toxicity of immunosuppressants [93,[105][106][107][108]. Other animals such as pig [109] and monkey [110][111][112] have also been used for islet autotransplantation and have shown acceptable outcomes.…”

“…Using fetal porcine allotransplantation and murine transplantation models, Stokes et al showed higher transplantation efficacy for spleen compared to liver, although kidney was better [127,128]. Many other studies have reported the superiority of spleen compared to liver [98,109] or omental pouch [54,129], although some groups have reported the opposite [95][96][97] (Table 3).…”