Tissue responses against immunoisolating alginate‐PLL capsules in the immediate posttransplant period

Abstract

Alginate-polylysine (PLL) capsules are commonly applied for immunoisolation of living cells for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by insufficient biocompatibility of the capsules with failure of the grafts as a consequence. Most studies addressing biocompatibility issues of alginate-PLL capsules have focused on the degree of overgrowth on the capsules after graft failure and not on the reaction against the capsules in the immediate posttransplant period. Therefore, capsules were implanted in the peritoneal cavity of rats and retrieved 1, 5, and 7 days later for histological examination and X-ray photoelectron spectroscopy analysis for evaluation of chemical changes at the capsule surface. After implantation, the nitrogen signal increased from 5% on day 0, to 8.6% on day 7, illustrating protein adsorption on the capsule's surface. This increase in protein content of the membrane was accompanied by an increase in the percentage of overgrown capsules from 0.5 +/- 0.3% on day 1 to 3.3 +/- 1.6% on day 7. The cellular overgrowth was composed of monocytes/macrophages, granulocytes, fibroblasts, erythrocytes, multinucleated giant cells, and basophils. This overgrowth was not statical as generally assumed but rather dynamic as illustrated by our observation that at day 1 after implantation we mainly found monocytes/macrophages and granulocytes that on later time points were substituted by fibroblasts. As the inflammatory reaction predictably interfere with survival of encapsulated cells, efforts should be made to suppress activities or recruitment of inflammatory cells. These efforts may be temporary rather than permanent because most inflammatory cells have disappeared after 2 weeks of implantation.

Survival of encapsulated islets: More than a membrane story

“…The process induces inflammatory responses immediately. These are manifested by cross activation of immune cells of the innate system (neutrophils, basophils, and macrophages [39] ). Once activated, these cells release bioactive cytokines [4042] in the vicinity of the graft that aim to heal the wound.…”

Avoiding Immunosuppression for Islet Transplantation: Use of Protective Biomaterials

“…In addition to cellular adhesion and PFO, death of encapsulated islets may also be caused by chemokines and cytokines that are small enough to pass through the permeable capsules [64]. TLRs, upon recognition and binding of PAMPS to the receptor surface, initiate an intracellular signaling cascade ultimately resulting in the secretion of a host of inflammatory cytokines attributed to translocation of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) into the nucleus [65].…”

Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials

“…that PAMP-activated macrophages, granulocytes, and basophils can cause deleterious effects through biologically active small molecules such as chemokines and cytokines secreted in the graft milieu [ 5 ]. Should the morphological properties of the device surfaces lend itself to cellular adhesion, graft viability may be lowered by PFO, but barring such properties, the same outcome may be provoked via secreted molecules capable of diffusing through the pores of the alginate matrices [ 5 ].…”

“…Should the morphological properties of the device surfaces lend itself to cellular adhesion, graft viability may be lowered by PFO, but barring such properties, the same outcome may be provoked via secreted molecules capable of diffusing through the pores of the alginate matrices [ 5 ].…”