No abstract

Background: There is a need for better strategies to promote burn wound healing and prevent infection. The aim of our study was to develop an easy-to-use placental multipotent mesenchymal stromal cell (MMSC) secretome-based chitosan hydrogel (MSC-Ch-gel) and estimate its antimicrobial and regenerative activity in Staphylococcus aureus-infected burn wounds in rats. Methods: Proteomic studies of the MMSC secretome revealed proteins involved in regeneration, angiogenesis, and defence responses. The MMSC secretome was collected from cultured cells and mixed with water-soluble chitosan to prepare the placental MSC-Ch-gel, which was stored in liquid phase at 4 °C. The wounds of rats with established II-IIIa-degree burns were then infected with S. aureus and externally covered with the MSC-Ch-gel. Three additional rat groups were treated with medical Vaseline oil, the antiseptic drug Miramistin®, or the drug Bepanthen® Plus. Skin wound samples were collected 4 and 8 days after burning for further microbiological and histological analysis. Blood samples were also collected for biochemical analysis. Results: Application of the MSC-Ch-gel cleared the wound of microorganisms (S. aureus wasn’t detected in the washings from the burned areas), decreased inflammation, enhanced re-epithelialisation, and promoted the formation of well-vascularised granulation tissue. Conclusions: MSC-Ch-gel effectively promotes infected wound healing in rats with third-degree burns. Gel preparation can be easily implemented into clinical practice.

Mesenchymal stromal precursor cells from human lipoaspirate (lMSC) cultured at 5% O(2) formed 50% less mineralized matrix in response to osteogenic induction than cells cultured under standard conditions (20% O(2)). After lMSC percultured at 5% O(2) were transferred to normoxic conditions (20% O(2)), they produced the same amount of matrix as lMSC permanently cultured at 20% O(2). Hence, hypoxia inhibited the commitment of lMSC under the effect of osteogenic stimuli, which can be important in reparative and regenerative medicine.

The effects of short-term (3 h) and long-term (18 h) repeated hypoxic exposure (5% O(2)) on viability of endothelial cells, expression of adhesion molecules, and secretion of IL-6 and vascular endothelial growth factor were studied. The resultant number of apoptotic and necrotic cells indicates that cultured endothelium well tolerates repeated changes in partial oxygen pressure in the medium, despite the stress reaction manifesting in enhanced secretion of IL-6. Changes in number of cells carrying ICAM-1 on their surface and activation of the synthesis of vascular endothelial growth factor during long-term exposure attest to activation of angiogenesis and inhibition of apoptosis.

Meso-Xanthin (Meso-Xanthin F199™) is a highly active antiaging injection drug of the latest generation. The main acting compound is fucoxanthin, supplemented with several growth factors, vitamins, and hyaluronic acid. Previous examination of fucoxanthin on melanocytes showed its ability to inhibit skin pigmentation through different signaling pathways focused on suppression of melanogenic-stimulating receptors. In turn, the anticancer property of fucoxanthin is realized through MAPK and PI3K pathways. We aimed to evaluate the effect of fucoxanthin and supplemented growth factors on melanocyte growth and transformation at a proteomic level. The effect of fucoxanthin on melanocytes cultivated in three-dimensional (3D) condition was examined using high-throughput proteomic and system biology approaches to disclose key molecular events of the targeted action. Our results demonstrated significant inhibition of cell differentiation and ubiquitination processes. We found that the negative regulation of PSME1 and PTGIS largely determines the inhibition of NF-κB and MAPK2. Besides, fucoxanthin selectively inhibits cell differentiation via negative regulation of Raf signaling and the upstream activation of IL-1 signaling. It is assumed that inhibition of Raf influences the Notch-4 signaling and switches off the MAPK/MAPK2 cascade. Blockage of MAPK/MAPK2 is feasible due to suppression of Ras and NF-κB by the addressed action of IKKB, IKK2, and TRAF6. Suggestively, Meso-Xanthin F199™ can manage processes of proliferative activity and inhibition of apoptosis due to composition of fucoxanthin and growth-stimulating factors, which may increase the risk of skin cancer development under certain condition.