STEREOTYPIC CULTURE SYSTEMS FOR LIVER AND BONE-MARROW - EVIDENCE FOR THE DEVELOPMENT OF FUNCTIONAL TISSUE IN-VITRO AND FOLLOWING IMPLANTATION IN-VIVO

Stromal cell-associated liver cell and bone marrow (BM) culture on three-dimensional nylon screen or polyglycolic acid (PGA) felt templates conveys certain functional advantages to the parenchyma of these tissues. Hepatic parenchymal cells (PC) manifest longterm (similar to 2 months) expression of liver-specific activities including cytochrome P450 enzyme activity and the synthesis of albumin, fibrinogen, transferrin, and other proteins. PC also undergo proliferation in association with stromal cells that were pre-established on these templates. PC mitoses are directly proportional to available space within the template for their expansion indicating that geometric or stereotypic parameters influence the growth of these cells in vitro. BM cultured on a similar template exhibits long-term multilineage hematopoietic expression and limited expansion of progenitor cell numbers. Progenitor cell concentration within the cultures can be substantially enhanced if these cells are liberated from co-culture and reseeded onto a template containing fresh stromal cells. BM and liver cell cultures established on felt composed of bioresorbable PGA filaments was grafted into various sites in rats. Liver co-cultures generated sinusoids and other liver-like structures in situ; active hematopoietic blasts were observed at sites of BM co-culture grafts. Biodegradable polymer constructs may prove useful for certain clinical applications as vehicles for the delivery of tissues that were engineered in culture. (C) 1994 John Wiley and Sons, Inc.