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Human macrophages (MF) express cytochrome P450 enzymes verifying their capacity to metabolize a variety of endogenous and exogenous substances. Here we analysed the mRNA and protein expression of transport proteins involved in the uptake or export of drugs, hormones and arachidonic acid metabolites in dendritic cells (DC) and MF compared to their precursors -blood monocytes -using cDNA microarray, RT-PCR, Western-blot and immunostaining techniques. The transport proteins studied included members of the solute carrier organic anion transporter family (SLCO) and the multidrug resistance associated proteins (MRP) 1-6 belonging to the ATP-binding cassette subfamily C (ABCC). We found that only mRNA for SLCO-2B1, -3A1, and -4A1 were present in monocytes, MF and DC. Most interestingly the expression of SLCO-2B1 was markedly enhanced in MF as compared to monocytes and DC. The presence of mRNA for ABCC1, 3, 4, 5 and 6 in all three cell types was demonstrated. On protein level ABCC1 ⁄ MRP1 which has been identified as leukotriene C 4 transporter was found to be the most abundant transporter in MF and DC. Blocking the ABCC1 ⁄ MRP1 activity with the specific inhibitor MK571 resulted in a phenotypic change in DC but not in MF. Our data show that human blood monocytes and monocyte derived MF as well as DC express a specific profile of transporters involved in uptake and export of exogenous molecules like allergens or drugs, but also of endogenous substances in particular of inflammatory lipid mediators like leukotrienes and prostaglandins.

According to data published by the Centers for Disease Control and Prevention, over 6 million people undergo a variety of medical procedures for the repair of articular cartilage defects in the U.S. each year. Trauma, tumor, and age-related degeneration can cause major defects in articular cartilage, which has a poor intrinsic capacity for healing. Therefore, there is substantial interest in the development of novel cartilage tissue engineering strategies to restore articular cartilage defects to a normal or prediseased state. Special attention has been paid to the expansion of chondrocytes, which produce and maintain the cartilaginous matrix in healthy cartilage. This review summarizes the current efforts to generate chondrocytes from adipose-derived stem cells (ASCs) and provides an outlook on promising future strategies.

To allow for a better implementation of external volume expansion to clinical applications for soft tissue regeneration, it is necessary to comprehensively understand the underlying mechanisms. As human adipose-derived stem cells (hASCs) play a crucial role in soft tissue enlargement, we investigated the impact of cyclic stretch on gene expression, proliferation rate and adipogenic differentiation of these cells. After cyclic stretching, RNA was extracted and subjected to DNA microarray analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Also, the expression of FABP4 mRNA was analysed by RT-qPCR to test whether mechanical stretch affected adipogenic differentiation of hASCs. The proliferation rate was assessed using the alamarBlue assay and Ki-67 staining. A cell cycle analysis was performed with flow cytometry and Western blot. We found that cyclic stretch significantly induced the expression of CYP1B1 mRNA. Furthermore, the adipogenic differentiation of hASCs was impaired, as was the proliferation. This was partly due to a decrease in extracellular signal-regulated kinase (ERK) 1/2 and histone H3 phosphorylation, suggesting a growth arrest in the G 2 /M phase of the cell cycle. Enrichment analyses demonstrated that stretch-regulated genes were over-represented in pathways and biological processes involved in extracellular matrix organization, vascular remodelling and responses to cell stress. Taken together, mechanical stress impaired both proliferation and adipogenic differentiation, but led to a tissue-remodelling phenotype of hASCs. These data suggest that extracellular matrix remodelling and neoangiogenesis may play a more important role in external volume expansion than proliferation and adipogenesis of hASCs.

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Background Although chemical antiseptics are the most basic measure to control wound infection and frequently come into contact with subcutaneous adipose tissue, no studies have evaluated their toxicity on adipose tissue and its cell fractions. In the present study, the effects of the following antiseptics on adipose-derived stem cells (ASC) were evaluated: Betaisodona® (povidone iodine), Lavasept®/Prontosan® (polyhexanide), Mafenide acetate, and Octenisept® (octenidinedihydrochloride). Methods Human ASCs were harvested from healthy donors. ASC viability was measured after treatment with different concentrations of antiseptics over five days. Furthermore, the effect on the proliferation, adipogenic differentiation, and apoptosis/necrosis of ASCs was analyzed. Finally, the mRNA expression of the stem cell markers CD29, CD34, CD73, CD90, and CD105 was detected. Results Octenisept® and Betaisodona® significantly reduced ASC proliferation and differentiation and led to considerable ASC necrosis. Octenisept® decreased ASC viability at the lowest concentrations tested and all stem cell markers were down-regulated by Octeniseptr® and Betaisodona®. Lavasept® and Prontosan® both led to reduced ASC viability, proliferation, differentiation, and increased apoptosis/necrosis, though the effects were less pronounced than those of Octenisept® and Betaisodona®. ASCs survived treatment with Mafenide acetate even at high concentrations, and Mafenide acetate showed minimal negative effects on their proliferation, adipogenic differentiation, cell death, and stem cell marker expression. Conclusion Mafenide acetate may be regarded as a feasible antiseptic for the treatment of wounds with exposed adipose tissue due to its low ASC toxicity. While Lavasept® and Prontosan® are possible alternatives, Octenisept® and Betaisodona® may only be used in highly diluted solutions.