A membrane-mimetic barrier for islet encapsulation.
BACKGROUND
Enhanced control of both transport properties and surface physiochemical characteristics will be important steps in the development of an effective immunoisolation barrier critical to the success of pancreatic islet cell transplantation. We hypothesize that the cell membrane establishes an important paradigm for the design of a biomimetic immunoisolation barrier with improved performance characteristics because of its capacity to control interfacial mass transport, as well as its ability to act as a template for more complex structures with other immunoregulatory macromolecules.


METHODS
Islets were isolated from Wistar rats using collagenase digestion and a discontinuous Ficoll-Histopaque gradient and subsequently encapsulated in 2% alginate. After coating with a polyelectrolyte multilayer of polylysine and alginate, a polymeric membrane-mimetic coating was applied to the capsule surface. Individual islet viability was evaluated at each stage of the encapsulation procedure by use of a two-color live/dead cell assay. Preservation of islet function was determined by transplanting 1000 encapsulated islets into the peritoneal cavity of streptozotocin-induced diabetic nonobese diabetic NOD/Scid mice.


RESULTS
At the end of the coating procedure, the proportion of viable cells within each islet was >50% in 88% of encapsulated rat islets and >75% in over half of the encapsulated cohort. Nonfasting blood glucose levels normalized within 24 hours after transplantation (n = 8). Normoglycemia has been maintained in all mice with the longest time course being 73 days thus far.


CONCLUSIONS
We have demonstrated that microencapsulated islets coated with a membrane-mimetic thin film can be generated with high viability in vitro and persistent function in vivo.
Cui
W
W
Department of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Barr
G
G
Faucher
K M
KM
Sun
X-L
XL
Safley
S A
SA
Weber
C J
CJ
Chaikof
E L
EL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002214:Capsules; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000502:physiology*; D006085:Graft Survival / Q000502:physiology; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001786:Blood Glucose; D002214:Capsules