RESUMO
Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells' 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells' reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC's interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate.
Assuntos
Comunicação Celular , Linhagem da Célula , Junções Célula-Matriz/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Amidas/farmacologia , Comunicação Celular/efeitos dos fármacos , Linhagem da Célula/efeitos dos fármacos , Junções Célula-Matriz/efeitos dos fármacos , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Paclitaxel/farmacologia , Piridinas/farmacologia , Células-Tronco/efeitos dos fármacosRESUMO
Aging is a multifactorial and natural process that causes physiological changes in organs, tissues and cells over time. In the skin and cartilage, aging leads to a decrease in the synthesis and changes in the arrangement of proteoglycans and collagen, in addition to the loss of glycosaminoglycans, which are responsible for the integrity and health of these tissues. We hypothesized that daily oral supplementation with a liquid nutraceutical containing hydrolyzed fish collagen, vitamins, antioxidants and other active ingredients could improve skin texture and elasticity, and in addition have a protective effect on joint health. A double-blind, randomized, placebo-controlled clinical trial was conducted on 120 subjects who consumed either the test product or placebo on a daily basis for 90â¯days. Subjects consuming the test product had an overall significant increase in skin elasticity (+40%; Pâ¯<â¯.0001) when compared to placebo. Histological analysis of skin biopsies revealed positive changes in the skin architecture, with a reduction in solar elastosis and improvement in collagen fiber organization in the test product group. As reported in the self-perception questionnaires, these results were confirmed by the subjects' own perceptions in that participants agreed their skin was more hydrated and more elastic. In addition, the consumption of the test product reduced joint pain by -43% and improved joint mobility by +39%. Oral supplementation with collagen bioactive peptides combined with chondroitin sulphate, glucosamine, L-carnitine, vitamins, and minerals significantly improved the clinical parameters related to skin aging and joint health, and therefore, might be an effective solution to slow down the hallmarks of aging.