Current progress and perspectives in immunoisolated islet transplantation

Abstract

This review summarizes the recent results of immunoioslated islet allo- and xenotransplants, especially in large animal species, and presents certain issues that would be important for the advancement of this technology toward clinical application. To date, the best results have been obtained with alginate microcapsules in both allo- and xenogeneic (porcine) islet transplantation in the spontaneously diabetic dogs and monkeys. Reversal of diabetes was also achieved in mice with cryopreserved, microencapsulated rat islets. However, results with these microcapsules have been highly variable and inconsistent from one laboratory to another. The causes of these discrepancies are multiple, but not totally understood. Immunoisolation devices have been investigated as an alternate approach to house a large number of islets in a space constructed by membranes of a defined pore size. Vascularized bioartificial devices were among the few cases that obtained long-term allo- and xenogeneic islet survival in totally pancreatectomized dogs. Thrombosis and associated problems were the major cause of failure with these devices. Diffusion chambers that have no vascular connection have been tested successfully in rodents, but no report has been available in large animal species. We have learned many important lessons and made considerable progress in islet immunoisolation. However, immunoisolated islet transplants have been only minimally successful in large animal models, and such technologies must be improved to achieve consistent success in large animal models prior to clinical trials. This will requires strict quality control of the islets, the membrane material, and the device construction. The membrane pore size that allows the permeation of molecules necessary for islet survival and function also permits the entry of cytokines, oxygen-radicals, and other small-size inflammatory products. Thus, the key to success appears to be to minimize inflammatory reactions generated by immuneisolation devices/capsules.

Modulation of peritendinous adhesion formation by alginate solution in a rabbit flexor tendon model

“…7,18 The best results have been obtained with alginate microcapsules in the field of allo-and xenogenic islet transplantation. 8 In cell encapsulation, alginate gel that is crosslinked with covalent bonds is generally applied. However, this has a hard consistency, making it unsuitable for application as a coatable or injectable tendon adhesion barrier gel.…”

“…7 In allo-and xenogeneic islet transplantation, the best results have been obtained with alginate microcapsules; success in this procedure was attained by enclosing grafts in a selectively permeable alginate membrane. 8 The membrane only allows the permeation of smaller molecules, such as oxygen, glucose and insulin, preventing the penetration of immunocytes and larger immune molecules. 8 We hypothesized that the same cell immobilization effect would occur in the application of alginate to injured tendon.…”

“…8 The membrane only allows the permeation of smaller molecules, such as oxygen, glucose and insulin, preventing the penetration of immunocytes and larger immune molecules. 8 We hypothesized that the same cell immobilization effect would occur in the application of alginate to injured tendon. The present study investigated whether a beneficial antiadhesive effect could be obtained using alginate solution on rabbit tendon injury.…”

Maintenance of aerobic metabolism increases immunoisolated islet survival

“…Much progress has been made in solving the problems of tissue reactivity to the chemical constituents of immunoisolation devices and the loss of islets housed in the devices from inflammatory and immune rejection processes. [1][2][3][4] However, the loss of islets from prolonged ischemia remains an obstacle to the success of islet immunoisolation as a treatment for diabetes. 1,3,4 Cytoglobin (Cygb) is an intracellular oxygen binding protein found in many mammalian tissues, including islet β-cells.…”

“…[1][2][3][4] However, the loss of islets from prolonged ischemia remains an obstacle to the success of islet immunoisolation as a treatment for diabetes. 1,3,4 Cytoglobin (Cygb) is an intracellular oxygen binding protein found in many mammalian tissues, including islet β-cells. 5 Cygb may act as an intracellular oxygen scavenger and may provide oxygen to mitochondria as well as cytoplasmic enzymes to inhibit the activation of apoptotic metabolic pathways.…”