Short-term immunosuppression reduces fibrotic cellular infiltration around barium-M-alginate microbeads injected intraportally.
BACKGROUND
One of the major barriers affecting the viability of encapsulated islets is pericapsular fibrotic infiltration (PFI). This study aimed to design strategies to reduce PFI around intraportally injected alginate microbeads.


METHODS
Empty, highly purified, barium-M-alginate microbeads (400 microm) were injected intraportally into Lewis rats (3000 beads/rat). Rats (n = 9/group) were treated daily with either rapamycine (RAPA; 1 mg/kg/d p.o.), tacrolimus (TAC; 2 mg/kg/d p.o.), a combination of both, or gadolinium-chloride (GdC13, 20 mg/kg/d i.v., at day -1 and day +4). Treatment was discontinued at 10 days. Three rats/group were sacrificed at 3, 7, and 42 days after transplantation. Cellular composition of PFI was evaluated by immunohistochemistry. Severity of the reaction to the beads was determined by measuring the thickness of PFI on histology.


RESULTS
The main cellular components of PFI in the liver were macrophages and myofibroblasts. There was a significant (P <.05) reduction in the thickness of PFI in all treated groups, even 6 weeks after transplantation. Encapsulated rat islets showed excellent insulin response to glucose in vitro, with a stimulation index of 3.6 +/- 2.0.


CONCLUSIONS
Combination of highly purified alginate with short-term immunosuppression reduces fibrotic overgrowth around microbeads injected intraportally.
Mathe
Z
Z
Cell Isolation and Transplantation Center, Geneva University Hospitals, Geneva, Switzerland.
Bucher
P
P
Bosco
D
D
Andres
A
A
Fux
C
C
Toso
C
C
Oberholzer
J
J
Wandrey
C
C
Sainz-Vidal
D
D
Espinosa
D
D
Bühler
L
L
Morel
P
P
Berney
T
T
D000464:Alginates; D000818:Animals; D002214:Capsules; D005355:Fibrosis / Q000517:prevention & control; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D011168:Portal System; D051381:Rats; D011917:Rats, Inbred Lew
D000464:Alginates; D002214:Capsules; D006603:Hexuronic Acids; D007166:Immunosuppressive Agents; D020723:Glucuronic Acid