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Int J Mol Sci ; 23(4)2022 Feb 19.
Article in English | MEDLINE | ID: covidwho-1715401


Obesity is an increasingly severe public health problem, which brings huge social and economic burdens. Increased body adiposity in obesity is not only tightly associated with type 2 diabetes, but also significantly increases the risks of other chronic diseases including cardiovascular diseases, fatty liver diseases and cancers. Adipogenesis describes the process of the differentiation and maturation of adipocytes, which accumulate in distributed adipose tissue at various sites in the body. The major functions of white adipocytes are to store energy as fat during periods when energy intake exceeds expenditure and to mobilize this stored fuel when energy expenditure exceeds intake. Brown/beige adipocytes contribute to non-shivering thermogenesis upon cold exposure and adrenergic stimulation, and thereby promote energy consumption. The imbalance of energy intake and expenditure causes obesity. Recent interest in epigenetics and signaling pathways has utilized small molecule tools aimed at modifying obesity-specific gene expression. In this review, we discuss compounds with adipogenesis-related signaling pathways and epigenetic modulating properties that have been identified as potential therapeutic agents which cast some light on the future treatment of obesity.

Adipogenesis/drug effects , Anti-Obesity Agents/pharmacology , Obesity/drug therapy , Adiposity/drug effects , Animals , Energy Metabolism/drug effects , Humans , Obesity/metabolism , Signal Transduction/drug effects , Thermogenesis/drug effects
Cytotherapy ; 22(8): 458-472, 2020 08.
Article in English | MEDLINE | ID: covidwho-209852


BACKGROUND AIMS: Human platelet lysate can replace fetal bovine serum (FBS) for xeno-free ex vivo expansion of mesenchymal stromal cells (MSCs), but pooling of platelet concentrates (PCs) increases risks of pathogen transmission. We evaluated the feasibility of performing nanofiltration of platelet lysates and determined the impact on expansion of bone marrow-derived MSCs. METHODS: Platelet lysates were prepared by freeze-thawing of pathogen-reduced (Intercept) PCs suspended in 65% storage solution (SPP+) and 35% plasma, and by serum-conversion of PCs suspended in 100% plasma. Lysates were added to the MSC growth media at 10% (v/v), filtered and subjected to cascade nanofiltration on 35- and 19-nm Planova filters. Media supplemented with 10% starting platelet lysates or FBS were used as the controls. Impacts of nanofiltration on the growth media composition, removal of platelet extracellular vesicles (PEVs) and MSC expansion were evaluated. RESULTS: Nanofiltration did not detrimentally affect contents of total protein and growth factors or the biochemical composition. The clearance factor of PEVs was >3 log values. Expansion, proliferation, membrane markers, differentiation potential and immunosuppressive properties of cells in nanofiltered media were consistently better than those expanded in FBS-supplemented media. Compared with FBS, chondrogenesis and osteogenesis genes were expressed more in nanofiltered media, and there were fewer senescent cells over six passages. CONCLUSIONS: Nanofiltration of growth media supplemented with two types of platelet lysates, including one prepared from pathogen-reduced PCs, is technically feasible. These data support the possibility of developing pathogen-reduced xeno-free growth media for clinical-grade propagation of human cells.

Blood Platelets/cytology , Cell Culture Techniques/methods , Filtration , Mesenchymal Stem Cells/cytology , Nanotechnology , Adipogenesis/drug effects , Biomarkers/metabolism , Cell Differentiation/drug effects , Cell Lineage/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Cellular Senescence/drug effects , Culture Media/pharmacology , Extracellular Vesicles/metabolism , Gene Expression Profiling , Humans , Immunophenotyping , Immunosuppression Therapy , Intercellular Signaling Peptides and Proteins/metabolism , Intercellular Signaling Peptides and Proteins/pharmacology , Mesenchymal Stem Cells/drug effects , Osteogenesis/drug effects , Particle Size , Serum/chemistry