Intraportal Transplantation of Allogenic Pancreatic Islets Encapsulated in Barium Alginate Beads in Diabetic Rats

Abstract

The survival of microencapsulated islets transplanted into the unmodified peritoneal cavity is limited, even if capsular overgrowth is restricted to a minimum, due to an insufficient oxygen supply to the islets. Therefore, research efforts should focus on finding or creating a transplantation site, which permits a closer contact between the encapsulated islets and the blood. For this reason, the liver could be an interesting candidate. The aim of the present study was to test the hypothesis that the intraportal transplantation of allogenic islets encapsulated in small-sized barium alginate beads is safe and succeeds to induce normoglycemia in diabetic rats. The intraportal transplantation of 1,500 islets encapsulated in barium alginate beads leads within 10 h and up to 24 h to blood sugar concentrations below 40 mg/dL, most likely due to an acute cell lysis of the graft. Afterwards, the reappearance of the diabetic state could be detected in these animals. Most likely these findings are induced by a sudden hypoxia to the islets. We believe that the occlusion of small- and medium-sized portal venules by the alginate beads is responsible for this effect. Therefore, in forthcoming studies, barium alginate beads, with a diameter below 350 micro m, stabilized with medical approved additives should be used.

Islet transplantation in rodents: do encapsulated islets really work?

“…Nonencapsulated islets may be injected into the liver (4,16,18,19,35,44,50,52) , kidney (5,14,15,16,17,24,27,28,32,34,35,42,46,47) , peritoneal cavity (11,35) , bone marrow (41) and subcutaneous tissue (22,48) . Ikebukuro et al (19) showed that islets and bone marrow cells, when injected into the liver using irradiation as immunosuppression, can increase the functionality of the cells for more than 365 days.…”

“…> 365 Spadella et al (50) 1500 365 Schneider et al (44) 1500 97 ± 2 Omer et al (35) 4000 70 Taira M. et al (52) 600 30 Ikebukuro et al (18) 600 250…”

“…14 Subcutaneous tissue Sorenby et al (48) 200 to 1000 ± 6 Sorenby et al (49) 125 to 375 28 Liver Schneider S. et al (44) (19) …”

Encapsulated islets transplantation: Past, present and future

“…Moreover, the infusion of islets with some other pancreatic tissues 23 February 15, 2012|Volume 3|Issue 1| WJGP|www.wjgnet.com (acinar cells, ductal cells or connective tissues) in the portal vein always has a risk of causing portal hypertension and portal vein embolization [71] . Schneider et al [72] transplanted microencapsulated rat islets (with alginate) into the livers of mice, but only a 1 wk normalization in the blood glucose level was achieved. We revealed [70] that transplanted islets suffer from ischemia due to embolization by the islets themselves.…”

Islet Encapsulation: Strategies to Enhance Islet Cell Functions

“…83 The liver has also been investigated as a possible transplant site for islet microcapsules. 84 It may be possible to transplant the islet microcapsules through an intra-portal injection, eliminating the need for surgical implantation of the encapsulated islets. 85,86 For these reasons, many researchers are investigating extra-peritoneal sites for the transplantation of islet cells.…”