Abstract
Islet transplantation as a biological β-cell replacement therapy has emerged as a
promising option for achieving restoration of metabolic control in type 1 diabetes
patients. However, partial or complete loss of islet graft function occurs in relatively
short time (months to few years) after implantation. The high rate of early transplant
dysfunction has been attributed to poorly viable and/or functional islets and is mediated
by innate inflammatory response at the intravascular (hepatic) transplant site and
critical lack of initial nutrient/oxygen supply prior to islet engraftment. In addition,
the diabetogenic effect of mandatory immunosuppressive agents, limited control of
alloimmunity, and the recurrence of autoimmunity limit the long-term success of islet
transplantation. In order to abrogate instant blood-mediated inflammatory reaction
and to provide oxygen supply for the islet graft, we have developed an extravascular
(subcutaneous) transplant macrochamber (the ‘βAir’ device). This device contains islets
immobilized in alginate, protected from the immune system by a thin hydrophilized
teflon membrane impregnated with alginate and supplied with oxygen by daily refueling
with oxygen-CO2 mixture. We have demonstrated successful utilization of the oxygen-refueling macrochamber
for sustained islet viability and function as well as immunoprotection after allogeneic
subcutaneous transplantation in healthy minipigs. Considering the current limitations
of intraportal islet engraftment and the restricted indication for islet transplantation
mainly due to necessary immunosuppressive therapy, this work could very likely lead
to remarkable improvements in the procedure and moreover opens up further strategies
for porcine islet cell xenotransplantation.
Key words
diabetes - new device - islet transplantation - encapsulation
References
Correspondence
barbara.ludwig@uniklinikum-dresden.de
