In vitro function of islets of Langerhans encapsulated with a membrane of porcine chondrocytes for immunoisolation.
OBJECTIVE
Widespread clinical application of islet transplantation remains restricted, because of insufficient methods to prevent rejection and autoimmune destruction of islet grafts. In this study we demonstrate long-term function of islets of Langerhans within a capsule of porcine chondrocytes which may serve as an immunoisolation barrier utilizing the immunoprivileged properties of the chondrocyte matrix.


METHODS
Islets of Langerhans were isolated from Lewis rats, seeded on biodegradable polyglycolic acid polymer, and encapsulated with a monolayer of porcine chondrocytes. The encapsulated constructs and controls were kept in culture for 5 weeks. One group was exposed to a glucose challenge every 5th day. The insulin concentration of the culture medium was measured. Histological and insulin-immunohistochemical studies were performed.


RESULTS
Hematoxylin and eosin histology demonstrated viability of the islets of Langerhans. The intact morphology was demonstrated by Heidenhain staining. Toluidine blue showed viability of surrounding chondrocyte layers. Immunohistochemistry was positive for insulin within the beta cells of the islets. Both encapsulated constructs and nonencapsulated controls showed increasing insulin levels after glucose challenge.


CONCLUSIONS
We can tissue engineer a chondrocyte encapsulation membrane which permits diffusion of glucose and insulin. Islets of Langerhans survive within the chondrocyte capsule, and the glucose/insulin feedback mechanism remains intact.
Pollok
J M
JM
Department of Hepatobiliary Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. pollock@uke.uni-hamburg.de
Lorenzen
M
M
Kölln
P A
PA
Török E
Kaufmann
P M
PM
Kluth
D
D
Bohuslavizki
K H
KH
Gundlach
M
M
Rogiers
X
X
D000818:Animals; D001672:Biocompatible Materials; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology*; D005947:Glucose; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D011100:Polyglycolic Acid; D051381:Rats; D011917:Rats, Inbred Lew; D013552:Swine; D014182:Transplantation, Autologous / Q000379:methods
D001672:Biocompatible Materials; D007328:Insulin; D011100:Polyglycolic Acid; D005947:Glucose