Embedding islet in a liquid scaffold increases islet viability and function.
BACKGROUND
Islet transplantation is a promising strategy to restore efficient insulin regulation in type 1 diabetes mellitus patients. However, shortage of islet donors, poor islet survival and toxicity of immunosuppressants often reduce the graft functional lifetime.


METHODS
We previously showed that a fibroblast populated-collagen matrix (CM) significantly improved engrafted islet viability/function. However, this composite was prone to gradual biodegradation and contraction. Moreover, to avoid use of systemic immunosuppressants, we proposed the use of a local immunosuppressive enzyme, indoleamine-2,3-dioxygenase (IDO). We developed a novel bioengineered crosslinked CM (CCM) to provide optimal matrix biomimetic. Viability and insulin secretory function of islets embedded within fibroblast populated CCM (FP-CCM) was evaluated in vitro and in vivo. IDO expression was transduced in fibroblasts by a lentiviral vector carrying IDO gene and islet viability was evaluated in the presence and absence of IDO producing cells.


RESULTS
Islet survival/function markedly improved within FP-CCM. Furthermore, our data shows that local lentiviral induction of IDO delivered by FP-CCM is nontoxic to the embedded islets.


CONCLUSIONS
This promising finding offers a new approach to improving islet transplant outcome.
Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
Azadeh
A
Hosseini-Tabatabaei
Reza Baradar
RB
Jalili
Ryan
R
Hartwell
Sanam
S
Salimi
Ruhangiz T
RT
Kilani
Aziz
A
Ghahary
D000818:Animals; D040761:Biomimetic Materials; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002470:Cell Survival; D003094:Collagen; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054457:Tissue Scaffolds
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D003094:Collagen
amino-indole 2,3– dioxygénase; crosslinked collagen matrix; greffe d’îlots; indoleamine-2,3-dioxygenase; islet transplantation; matrice collagène réticulée