Macrophage depletion improves survival of porcine neonatal pancreatic cell clusters contained in alginate macrocapsules transplanted into rats.
BACKGROUND
Macrophages can accumulate on the surface of empty and islet-containing alginate capsules, leading to loss of functional tissue. In this study, the effect of peritoneal macrophage depletion on the biocompatibility of alginate macrocapsules and function of macroencapsulated porcine neonatal pancreatic cell clusters (NPCCs) was investigated.


METHODS
Clodronate liposomes were injected into the peritoneal cavities of normoglycemic Lewis rats 5 and 2 days before the transplantation. Empty or NPCC-containing Ca-alginate poly L-lysine (PLL)-coated macrocapsules were transplanted into the peritoneal cavities of rats injected with either clodronate liposomes or saline. On days 7, 14 and 21, samples were evaluated by immunohistochemistry for cellular immune responses on the surface of the macrocapsules and for macrophage populations in omental tissue. To assess the function of macroencapsulated NPCCs, insulin secretory responses to glucose and theophylline were measured after capsule retrieval.


RESULTS
In saline-injected control groups, all of the empty and NPCC-containing macrocapsules were overgrown with macrophages, this being especially severe on NPCC-containing macrocapsules. In the clodronate liposomes-injected group, the majority of the empty macrocapsules were free of macrophage accumulation and the NPCC-containing macrocapsules were less overgrown than in control animals. Higher insulin responses to glucose and theophylline were observed in NPCCs retrieved from rats injected with clodronate liposomes.


CONCLUSIONS
We conclude that depletion of peritoneal macrophages with clodronate liposomes improve the survival of macroencapsulated NPCCs.
Omer
Abdulkadir
A
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Keegan
Mitchell
M
Czismadia
Eva
E
De Vos
Paul
P
Van Rooijen
Nico
N
Bonner-Weir
Susan
S
Weir
Gordon C
GC
D000464:Alginates; D000818:Animals; D000831:Animals, Newborn; D002214:Capsules; D002455:Cell Division; D004002:Clodronic Acid / Q000494:pharmacology; D006085:Graft Survival / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods*; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000276:immunology*; D016035:Pancreas Transplantation / Q000276:immunology* / Q000379:methods / Q000473:pathology; D051381:Rats; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000379:methods / Q000473:pathology
D000464:Alginates; D002214:Capsules; D008081:Liposomes; D004002:Clodronic Acid