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Cultivation under hypoxia has beneficial effects on adipose-derived stem cells (ASCs). Despite a history of extensive research on the responses of ASCs to hypoxia, investigations have focused on functional alterations of ASCs. Therefore, we provide novel insight in this review into the cellular and molecular changes that occur in ASCs under hypoxic conditions. Hypoxia increases the proliferation and migration of ASCs by the generation of reactive oxygen species (ROS) and downstream phosphorylation of platelet-derived growth factor receptor-beta, ERK1/2, and Akt. Chronically, activation of these signaling pathways upregulates miR-210 via phosphorylation of NF-κB and Elk1. Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) is a direct miR-210 target, and downregulation of PTPN2 mediates the proliferation and migration of ASCs during hypoxia. In addition, the paracrine effect of ASCs is enhanced under hypoxic conditions, irrespective of whether ROS are generated. Hypoxic preconditioning stabilizes hypoxia inducible factor-1α under hypoxic conditions and increases secretion of vascular endothelial growth factor, thereby improving the regenerative potential of ASCs. Therefore, understanding the cellular and molecular changes that occur during hypoxia is highly relevant for the development of novel ASC therapies.

In search of novel antipigmentation agents, a set of 3,840 compounds with natural-like synthetic or natural origin were screened against Kit (stem cell factor receptor). Emodin from the seed of Cassia tora and baicalin from Scutellariae radix showed potent inhibitory effects (IC(50) = 4.9 and 9.0 microM, respectively) on the phosphorylation of Kit. Emodin also blocked other receptor tyrosine kinase activities, such as epithelial growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR-2), fibroblast growth factor receptor 1 (FGFR-1), platelet-derived growth factor receptor b (PDGFR-b). In contrast to emodin, aloe-emodin did not inhibit Kit activity at all. Emodin also blocked the cellular kinase activities of Kit and its down-stream p44/42 mitogen activated protein kinase (MAPK) in MO7e cells and human primary melanocytes. Emodin strongly suppressed the melanin synthesis triggered by stem cell factor (SCF) treatment. Also, emodin showed almost no toxicity up to 10 microM on cultured melanocytes as reported previously by other researchers. The results indicate that emodin is a good candidate for the development of antipigmentation agents since it can radically block the differentiation and proliferation of pigment cells by reducing Kit signaling.