Ba. Naughton et al., STEREOTYPIC CULTURE SYSTEMS FOR LIVER AND BONE-MARROW - EVIDENCE FOR THE DEVELOPMENT OF FUNCTIONAL TISSUE IN-VITRO AND FOLLOWING IMPLANTATION IN-VIVO, Biotechnology and bioengineering, 43(8), 1994, pp. 810-825
Stromal cell-associated liver cell and bone marrow (BM) culture on thr
ee-dimensional nylon screen or polyglycolic acid (PGA) felt templates
conveys certain functional advantages to the parenchyma of these tissu
es. Hepatic parenchymal cells (PC) manifest longterm (similar to 2 mon
ths) 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 wit
h stromal cells that were pre-established on these templates. PC mitos
es are directly proportional to available space within the template fo
r 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 concent
ration within the cultures can be substantially enhanced if these cell
s are liberated from co-culture and reseeded onto a template containin
g 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 s
tructures in situ; active hematopoietic blasts were observed at sites
of BM co-culture grafts. Biodegradable polymer constructs may prove us
eful for certain clinical applications as vehicles for the delivery of
tissues that were engineered in culture. (C) 1994 John Wiley and Sons
, Inc.