NOVEL DELIVERY SYSTEM FOR INDUCING QUIESCENCE IN INTESTINAL STEM-CELLS IN RATS BY TRANSFORMING GROWTH-FACTOR BETA(1)

Background/Aims: Intestinal mucosa, a tissue in a dynamic state of rap id cellular proliferation, is often adversely affected by cytotoxic dr ugs. The purpose of this study was to develop an oral delivery system targeting transforming growth factor (TGF) beta 1 locally and analyze its effects on the epithelial stem cells of gastrointestinal mucosa. M ethods: Rats were treated with recombinant TGF-beta 1 in alginate bead s perorally or with recombinant TGF-beta 1 in phosphate-buffered salin e perorally or intraperitoneally. Control animals received phosphate-b uffered saline only. The size of the villi was measured. Proliferating and mitotic indices were determined by quantifying immunohistochemica l staining for proliferating cell nuclear antigen. Results: Alginate b eads released no TCF-beta 1 in acid. However, in pH 7.4, TGF-beta 1 wa s released in an active form. Histomorphometrical analysis showed a ma rked reduction in villus height (50%-70%) in the intestinal mucosa of animals treated perorally with recombinant TGF-beta 1 in alginate bead s. Also, the proliferating and mitotic indices were significantly redu ced (P < 0.01.) in these animals as compared with controls and other r outes of administration. Conclusions: This study shows that recombinan t TGF-beta 1 administered using a novel oral delivery system induces s tem cell quiescence in the intestinal mucosa of the rat.