Attenuation of cysteinyl leukotrienes induces human mesenchymal stem cell differentiation.

Although there are numerous investigations describing bone marrow cells or bone-marrow derived cells at the site of such injuries as bone fractures, infarction and subsequent ischemic reperfusion injury, or cutaneous wounds, little is know about the factors that affect the cells in those clinical situations. Cysteinyl leukotrienes have been extensively investigated in airway diseases that may eventually lead to lung fibrosis; while the engraftment of mesenchymal stem cells have been shown to reverse bleomycin-induced lung fibrosis in vivo. Therefore, we elucidated the involvement of cysteinyl leukotrienes in human mesenchymal stem cell proliferation and differentiation. Human mesenchymal stem cells express the cysteinyl leukotriene type 1 receptor. Various doses of pranlukast, which is a specific cysteinyl leukotriene type 1 receptor antagonist, failed to affect the proliferation of cells; however, 10(-6) M of pranlukast significantly induced cellular cytoplasmic differentiation by showing microvilli sprouting and the emersion of rough endoplasmic reticulum within a 16-hour(s) incubation. Additionally, pranlukast-induced fibronectin protein production by human mesenchymal stem cells. Therefore, attenuation of the cysteinyl leukotriene pathway contributes to human mesenchymal stem cell differentiation and may contribute to modulation of the local injury site.