Specific fibrinogen and thrombin concentrations promote neuronal rather than glial growth when primary neural cells are seeded within plasma-derived fibrin gels

Abstract

Fibrin gels are attractive scaffolds useful for neural tissue engineering applications. The objective of this work was to investigate the apoptotic activity, survival, proliferation, and differentiation of a mixed population of primary neural cells composed of neurons and multipotent precursor cells when cultured in fibrin gels prepared with varying concentrations of fibrinogen (5-25 mg/mL fibrinogen) and thrombin (1-125 U/mL thrombin). Within all fibrin gel formulations tested, the level of apoptosis on day 1 was low and cell survival was equivalent to levels in monolayer culture (67%). Proliferation in gels made from 5 to 12.5 mg/mL fibrinogen was also similar to that observed in monolayer culture, though a lower proliferative response was observed in 25 mg/mL fibrinogen formulations. Relative to monolayer culture, cholinergic and dopaminergic neuronal presence was enhanced, whereas glial cell growth was reduced in fibrin gel cultures. The extent to which levels were altered depended on fibrinogen and thrombin concentration. The findings here suggest the importance of fibrinogen and thrombin concentration in differentially regulating the growth and composition of neural cell populations and are of importance for neural tissue engineering strategies focused on the development of implantable scaffolds for treating neurodegenerative disorders.