The Cellular Adhesion And The Effect Factors Following Alginate-polycation Microcapsule Transplantation In The Peritoneal Cavity

Cell microencapsulation technology holds great promise for treating type 1diabetes mellitus, supporting hormone therapy, repairing the myocardium, and improving angiogenesis. While the therapeutic efficacy of microcapsules has been demonstrated, transplanted cells appear to be short-lived. Short microcapsule survival time is largely due to adherence of cells to the outer surface with proliferation and formation of an outer cellular layer. Current strategies to prolong survival time are designed to inhibit cell adhesion to the outside surface of the microcapsules. Adhesion prevention strategies described to date have included use of optimized or purified materials, without obvious effect. In this paper we examine the host response to microencapsulated cellular transplantation, mechanisms of cellular adhesion to the outer surface of microcapsules, and potential methods for reducing cellular adhesion to microcapsules.Alginate/polylysine/alginate (APA) and alginate/chitosan/alginate (ACA) microcapsules were transplanted into the peritoneal cavities of C57BL/6 mice. Transplantation of empty, cell-loading, tandem, or broken microcapsules did not evokea systemic inflammatory response, immunotoxicity, or, liver and kidney toxicity, suggesting that transplantation of normal, tandem, or broken microcapsules is safe. APA and ACA microcapsules were also used to study rejection of microcapsules after transplantation into the peritoneal cavities of C57BL/6 mice by assessing local inflammatory response, morphological changes, and changes in cell-adhesion. Following transplantation, inflammatory cells peaked on day 1 and cytokines peaked on day 7. The inflammatory response appeared to subside by day 14 when the cell adhesion entered into a stable period. These findings suggest that the rules of microcapsule transplantation are consistent with rejection rules for organ transplantation.Transplantation of ACA microcapsules into the peritoneal cavity of C57BL/6 mice was further used to study factors known to influence cellular adhesion to microcapsules C57BL/6 by multiple factor correlation and regression analysis. Microcapsule dose and rate of cellular adhesion to microcapsules were negatively correlated with lymphocyte count, IL-6 levels, and retrieval of free-floating microcapsules. In contrast, microcapsule dose and rate of cellular adhesions were positively correlated with macrophage and lymphocyte counts, levels of IL-6, IL-10, and MCP-1.Negative correlations were observed between lymphocyte counts and retrieval rate of free-floating microcapsules (RRf); amount of IL-6 and RRf, microcapsule dose and cell-adhesion rate on microcapsules (CR). In contrast, positive correlations were observed between macrophage and CR; lymphocyte counts CR; amount of IL-6 and CR; IL-10 and CR; MCP-1 and CR, microcapsule dose and RRf.Finally, methods for optimizing transplantation of microcapsules based on known cell adhesion mechanisms were tested, including short-term administration of glucocorticoid, cotransplantation of encapsulated mesenchymal stem cells and injection of medical-grade sodium hyaluronate. All three methods increased retrieval rate of free floating microcapsules and decreased the rate of cellular adhesion to the microcapsules and may offer potential methods for optimization of encapsulated cell transplantation treatments.The results presented here establish a foundation for reducing cellular adhesion to microcapsules with the potential to prolong graft survival and improve the efficacy of these treatments.