Defining Critical Parameters for Producing and Modulating Inflammation Caused by Cell Encapsulating Alginate Microspheres
Breger, Joyce Catherine
Wang, Nam Sun
Lyle, Dan B
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Minimizing induced inflammation, particularly nitric oxide (NO) production, is critical to optimal function or failure of implanted encapsulated cells. The purpose of this study is to define critical factors that affect toxic NO production from the macrophage cell line RAW264.7 in response to alginate microcapsules. The effects of the following were determined: 1) concentration of endotoxin (LPS) contamination; 2) presence of interferon-gamma (IFN-γ); 3) bead diameter and alginate volume; and 4) anti-inflammatory drugs in the alginate. A higher concentration (5 X) of LPS was required in alginate to produce the effect seen by LPS free in medium, sensitivity was enhanced by IFN-γ, bead diameter was inversely proportional to NO2 under low inflammatory conditions, and parthenolide in alginate significantly reduced inflammation. These results suggest that survival of implanted encapsulated cells may be improved by using highly purified alginate, avoiding ancillary inflammation, controlling surface area presentation, and incorporating anti-inflammatory drugs into the capsule matrix.