Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids.
Transplantation of encapsulated living cells is a promising approach for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by inflammatory responses against the capsules. In the present study, we investigate whether tissue responses against alginate-PLL-alginate capsules can be modulated by co-encapsulation and temporary release of immunomodulating factors such as dexamethasone. Such an approach may be mandatory in order to increase the function and survival of encapsulated tissue since it has been shown that the tissue response can be caused by many, insurmountable factors. In an in vitro assay, we demonstrated an antiproliferative effect of dexamethasone-containing capsules on L929-mouse-fibroblasts. Subsequently, capsules prepared of purified alginate with or without solved dexamethasone were implanted in the peritoneal cavity of rats and retrieved one month later for histological evaluation. Most of the capsules without dexamethasone proved to be overgrown and adherent to the abdominal organs whereas with co-encapsulated dexamethasone the majority of the capsules were found freely floating in the peritoneal cavity without overgrowth. We conclude that co-encapsulation of dexamethasone has a profound effect on fibroblasts and macrophages adherence to immunoisolating capsules.
Bünger
C M
CM
Department of Surgery, University of Rostock, Schillingallee 35, D-18055 Rostock, Germany. carsten.buenger@medizin.uni-rostock.de
Tiefenbach
B
B
Jahnke
A
A
Gerlach
C
C
Freier
Th
T
Schmitz
K P
KP
Hopt
U T
UT
Schareck
W
W
Klar
E
E
de Vos
P
P
D000464:Alginates / Q000009:adverse effects* / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000009:adverse effects* / Q000737:chemistry; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry; D004343:Drug Implants / Q000008:administration & dosage*; D004347:Drug Interactions; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D008422:Materials Testing; D051379:Mice; D011107:Polylysine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000737:chemistry; D013256:Steroids / Q000008:administration & dosage / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods*
D000464:Alginates; D000893:Anti-Inflammatory Agents; D020099:Coated Materials, Biocompatible; D004343:Drug Implants; D013256:Steroids; C051546:alginate-polylysine-alginate; D011107:Polylysine; D003907:Dexamethasone