sepharose and Foreign-Bodies

Biocompatibility of cell-enclosing capsules, defined as suppression of pericapsular cellular reactions, is one of the factors governing the success of enclosed cell transplantation in in vivo cell therapy. Agarose capsules of subsieve size, less than 100 microm in diameter, and conventional size, approximately 300-1,000 microm in diameter, were implanted into the peritoneal cavity and epididymal fat pads of mice and rats, respectively, to determine the effect of a reduction in diameter to subsieve size. The degree of cellular reaction to the subsieve-size capsules was much lower than that of the conventional-size microcapsules, independent of implantation site. The frequency of overgrown subsieve-size capsules retrieved from the peritoneal cavities was less than 5% in contrast to approximately 20% for capsules 387 microm in diameter. In addition, no increase in floating cells, which are generated through capsule stimulation, was observed in the peritoneal cavity only with subsieve-size capsules. From these results, we concluded that subsieve-size capsules are more biocompatible than microcapsules of conventional size.

Topics: Adipose Tissue; Animals; Biocompatible Materials; Capsules; Epididymis; Equipment Design; Foreign Bodies; Male; Rats; Sepharose

We hypothesized that foreign bodies in airways cause inflammation leading to goblet cell metaplasia. Instilled agarose plugs lodged in the bronchi of pathogen-free rats caused a time-dependent increase in Alcian blue-periodic acid-Schiff staining that was detected within 24 h and markedly increased at 72 h. Control bronchi contained no pregoblet or goblet cells, but plugged bronchi contained many pregoblet and goblet cells and a decrease in nongranulated secretory cells. In situ hybridization showed no expression of MUC5AC in control airways, but plugged airways showed a marked expression. Control bronchi showed sparse staining for epidermal growth factor receptor (EGFR) protein, but plugged bronchi showed intense EGFR staining in the epithelium. Pretreatment with an EGFR tyrosine kinase inhibitor (BIBX1522) prevented Alcian blue-periodic acid-Schiff staining and MUC5AC gene expression in plugged bronchi. Pretreatment with tumor necrosis factor-alpha neutralizing antibody or pretreatment with cyclophosphamide abolished plug-induced EGFR protein expression and goblet cell metaplasia. Thus instillation of agarose plugs induces profound goblet cell metaplasia by causing EGFR expression and activation.

Topics: Animals; Antibodies; Bronchi; Bronchitis; Cyclophosphamide; Enzyme Inhibitors; Epithelium; ErbB Receptors; Foreign Bodies; Gene Expression; Goblet Cells; Male; Metaplasia; Mucins; Protein-Tyrosine Kinases; Rats; Rats, Inbred F344; Sepharose; Tumor Necrosis Factor-alpha