This revised AREA grant describes a cell-polymer system for cell transplantation. The ultimate goal of this and future studies is to develop cell-polymer constructs with cells of pancreatic islets of Langherhans for the treatment of diabetes. Cells placed on a 3-D matrix have a surface on which to attach allowing them to organize, proliferate, and function. The total number of implanted cells can thus be increased compared to cell transplantation. Cells on the constructs, once implanted, can be nourished by diffusion, promote vascular ingrowth, and allow cells to proliferate and function. Preliminary studies by the P.I. indicate the feasibility of such implants using chondrocytes and isolated rat islet cells. We propose using rodent beta-cell lines HIT-T15 or RINm5F, for initial in vitro studies. These cell lines can be maintained in culture for up to 2 years (HIT-T15) and eliminate the problems associated with isolating and culturing primary islets. HIT-or RIN-cells will be seeded on available biodegradable, biocompatible polyglycolic acid or co-polymer of polylactic and polyglycolic acids. Viability and attachment assays will be performed to assess adhesion of the cells to the polymers. Insulin response to a stimulus will be a measure of cell function. Polymers may be coated with collagen, gelatin, fibronectin, laminin, or polylysine to enhance adhesion. We will then repeat the studies using isolated rat islets and determine cell function and adhesion to the polymers. If time allows, preliminary experiments to a more extensive study will be done to determine if pancreatic islet cells on polymers are functioning in vivo by measuring reversal of streptozocin-induced diabetes in rats. We hope to contribute to the fields of islet cell transplantation and diabetes, acquire general information about cell-polymer constructs, and provide valuable research opportunities to Barnard women interested in chemistry and biology.
