Characterization of several effectors on proliferation and differentiation potential of airway basal stem cells

Objective To clarify the effects of cellular components, cytokines and signal transduction molecules on the proliferation and differentiation potential of airway basal stem cells (ABSCs) in vitro. Methods The extracellular matrix substitute Matrigel three-dimensional culture system in vitro and immunohistochemical analysis were used to observe the effects of several common factors which played an important role in the proliferation and differentiation of stem cells on the number and size of colonies and differentiation potential of ABSCs. Results Compared with endothelial cells, fibroblasts increased the proliferation and differentiation potential of ABSCs.Fibroblast growth factor (FGFs) increased the number and diameter of ABSCs colonies in vitro, and induced them to differentiate into secretory cells.When the antagonists of FGFs and its receptor were treated, and the colony proliferation effect induced by FGFs disappeared.After treated with LIF, ALK5-I or ROCK-I, the number and diameter of ABSCs colonies also increased significantly and they were induced to differentiate into ciliated epithelial cells or secretory cells. Conclusions Mouse ABSCs does not depend on fibroblasts, but co-culture with fibroblasts can enhance their proliferation and differentiation ability.Endothelial cells limitedly promote the proliferation and differentiation of ABSCs.When treated with FGFs, LIF, ALK5-I or ROCK-I, the proliferation and differentiation of ABSCs are increased.Our results lay a foundation for the further study of ABSCs and shed light on the clinical research and application of airway regenerative medicine in the future. Key words: Trachea; Airway basal stem cells; Proliferation; Differentiation