INFLUENCE OF CELL-INTERACTIONS IN A NOVEL MODEL OF POSTNATAL MUCOSAL REGENERATION

Background and aims-Conventional models of postnatal mucosal regenerat ion are cumbersome and limited: a novel model is described here. In ad dition, the influence of cell interactions on mucosal regeneration is examined within the model. Methods-Postnatal rat small intestinal muco sa was digested by enzymes to yield heterotypic cell aggregates (CA). CA colony forming ability, growth, and limited cytodifferentiation wer e assessed in vitro. CA were transplanted subcutaneously and retrieved for histological examination at staggered intervals to assess neomuco sal morphogenesis and cytodifferentiation in vivo. Cell interactions i n CA were disrupted by enzymes, thus producing cell suspensions (CS). Regeneration by CA and CS were compared. Results-CA produced prolifera tive colonies in vitro and showed a temporal sequence of neomucosal mo rphogenesis and differentiation in vivo. CA colonies were more numerou s within 24 hours of primary culture and had greater cellularity by 96 hours than CS colonies. Alkaline phosphatase was expressed only by 25 8 of 696 CA colonies (37%). CA subcutaneous grafts (48 of 56 (87%)) re generated small intestinal neomucosa while CS were unsuccessful. Concl usion-These methods provide a model of mucosal regeneration which incl udes constituent processes of colony formation, growth, neomucosal mor phogenesis, and cytodifferentiation. Preservation of cell interactions within CA seems advantageous to regeneration sithin the model.