The results of this study may indicate that human mesenchymal stem cells participate and recruit in keloid pathogenesis by differentiating themselves toward keloid recalcitrant formation and progression.

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Cell-to-cell interactions between human mesenchymal stem cells and potential adjacent cells such as endothelial cells, dermal fibroblasts, and epidermal keratinocytes was investigated. A modified dual Boyden chamber assay using 8-microm pores revealed a more powerful chemotactic cell migration of human mesenchymal stem cells toward human epidermal keratinocytes than other cells, such as umbilical artery endothelial cells and dermal fibroblasts, during 16 hours of incubation (336.2+/-52.33, 36.0+/-11.20, and 62.7+/-18.16, cells/field, respectively, p<0.01; comparison between endothelial cells and keratinocytes, and fibroblasts and keratinocytes). Scanning electron microscopy showed human mesenchymal stem cell migration through the pores, with endothelial cells, fibroblasts, or keratinocytes in the lower chambers. Mesenchymal stem cell ultrastructural changes occurred, including a larger euchromatin nucleus, when the cells were placed in medium containing 10 percent fetal bovine serum, whereas basic fibroblast growth factor maintained the immature cell morphology for 4 days. Monolayer coculture also showed human mesenchymal stem cell changes in ultrastructural morphology in the vicinity of the epidermal keratinocytes. These data suggest that human mesenchymal stem cells may interact with human epidermal keratinocytes to accelerate wound healing and coverage.

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.

Parasympathetic nerve (PSN) innervates taste cells of the frog taste disk, and electrical stimulation of PSN elicited a slow hyperpolarizing potential (HP) in taste cells. Here we report that gustatory receptor potentials in frog taste cells are depressed by PSN-induced slow HPs. When PSN was stimulated at 30 Hz during generation of taste cell responses, the large amplitude of depolarizing receptor potential for 1 M NaCl and 1 mM acetic acid was depressed by approximately 40% by slow HPs, but the small amplitude of the depolarizing receptor potential for 10 mM quinine-HCl (Q-HCl) and 1 M sucrose was completely depressed by slow HPs and furthermore changed to the hyperpolarizing direction. The duration of the depolarizing receptor potentials depressed by slow HPs prolonged with increasing period of PSN stimulation. As tastant-induced depolarizing receptor potentials were increased, the amplitude of PSN-induced slow HPs inhibiting the receptor potentials gradually decreased. The mean reversal potentials of the slow HPs were approximately -1 mV under NaCl and acetic acid stimulations, but approximately -14 mV under Q-HCl and sucrose stimulations. This implies that when a slow HP was evoked on the same amplitude of depolarizing receptor potentials, the depression of the NaCl and acetic acid responses in taste cells was larger than that of Q-HCl and sucrose responses. It is concluded that slow HP-induced depression of gustatory depolarizing receptor potentials derives from the interaction between gustatory receptor current and slow hyperpolarizing current in frog taste cells and that the interaction is stronger for NaCl and acetic acid stimulations than for Q-HCl and sucrose stimulations.