INJECTABLE ALGINATE SEEDED WITH CHONDROCYTES AS A POTENTIAL TREATMENTFOR VESICOURETERAL REFLUX

Injection of polytetrafluoroethylene (Teflon) or collagen has been use d in the endoscopic treatment of vesicoureteral reflux. Although the p rinciple of an endoscopic treatment is valid, there are concerns regar ding the long-term safety and effectiveness of these substances. The g oal of several investigators has been to find alternate implant materi als that would be safe for human use. Toward this goal we conducted a study to determine the effect of chondrocytes using a biodegradable po lymer solution as a template. Hyaline cartilage was obtained from the articular surfaces of calf shoulders and chondrocytes were harvested. Chondrocyte suspensions were concentrated to 20, 30 and 40 x 10(6) cel ls per cc and mixed with dry alginate powder (a biodegradable polymer) to form a gel. Twelve athymic mice were injected subcutaneously with a chondrocyte-alginate solution. Each mouse had 4 injection sites, con sisting of control, 10, 15 and 20 x 10(6) chondrocyte cells (48 inject ion sites). Mice were sacrificed at 2, 4, 6 and 12 weeks after injecti on. Histological examination of the injection sites demonstrated evide nce of cartilage formation in 34 of the 36 experimental injection site s. Gross examination of the injection sites with increasing time showe d that the polymer gels were progressively replaced by cartilage. The ultimate size of the cartilage formed was related to the initial chond rocyte concentration injected, and appeared to be uniform and stable w ithin each category. There was no evidence of cartilage formation in t he 12 controls. Histological analyses of distant organs showed no evid ence of cartilage or alginate gel migration, or granuloma formation. I n conclusion, chondrocyte-alginate gel suspensions are injectable, app ear to be nonmigratory and are able to conserve their volume. In addit ion, the use of autologous cartilage cells would preclude an immunolog ical reaction. These preliminary studies indicate that autologous cart ilage-polymer gel solutions may be potentially useful in the endoscopi c treatment of reflux.