Orchestrating stem cell fate: Novel tools for regenerative medicine

et al. 2020

Cells

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Natural cosmetic products have recently re-emerged as a novel tool able to counteract skin aging and skin related damages. In addition, recently achieved progress in nanomedicine opens a novel approach yielding from combination of modern nanotechnology with traditional treatment for innovative pharmacotherapeutics. In the present study, we investigated the antiaging effect of a pretreatment with Myrtus communis natural extract combined with a polycaprolactone nanofibrous scaffold (NanoPCL-M) on skin cell populations exposed to UV. We set up a novel model of skin on a bioreactor mimicking a crosstalk between keratinocytes, stem cells and fibroblasts, as in skin. Beta-galactosidase assay, indicating the amount of senescent cells, and viability assay, revealed that fibroblasts and stem cells pretreated with NanoPCL-M and then exposed to UV are superimposable to control cells, untreated and unexposed to UV damage. On the other hand, cells only exposed to UV stress, without NanoPCL-M pretreatment, exhibited a significantly higher yield of senescent elements. Keratinocyte-based 3D structures appeared disjointed after UV-stress, as compared to NanoPCL-M pretreated samples. Gene expression analysis performed on different senescence associated genes, revealed the activation of a molecular program of rejuvenation in stem cells pretreated with NanoPCL-M and then exposed to UV. Altogether, our results highlight a future translational application of NanoPCL-M to prevent skin aging.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Smart Nanofibers with Natural Extracts Prevent Senescence Patterning in a Dynamic Cell Culture Model of Human Skin

Bellu

et al. 2020

Cells

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“…Adipose-derived stem cells (ADSCs) are one of the most promising cells for regenerative medicine, due to their higher differentiation potential and easy propagation, as compared to other sources [ 1 , 2 ]. These cells, located in the stromal vascular fraction (SVF) of adipose tissue, exert a central role during adipogenesis, differentiating to produce mature adipocytes [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Tuning Adipogenic Differentiation in ADSCs by Metformin and Vitamin D: Involvement of miRNAs

Balzano

et al. 2020

IJMS

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Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of specific genes. In addition, miRNAs are important modulating factors in obesity and numerous diseases. We previously identified specific conditioned media able to commit stem cells towards defined cellular phenotypes. In the present paper, we aimed at evaluating the role of metformin on ADSCs differentiation. In particular, ADSCs were cultured in a specific adipogenic conditioned medium (MD), in the presence of metformin, alone or in combination with vitamin D. Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4. We then evaluated the role of specific epigenetic modulating genes and miRNAs in controlling stem cell adipogenesis. The combination of the two molecules was able to influence stem cell fate, by modulating the adipogenic phenotype, suggesting their possible application in clinical practice in counteracting uncontrolled lipogenesis and obesity-related diseases.

“…ROS have been recognized as toxic and harmful by-products for stem cells, resulting in DNA damage, premature senescence or cell death [22]. MSCs are largely known for their ability to restore tissue function and differentiate into several phenotypes under appropriate stimuli [23], including osteogenic, chondrogenic, cardiogenic and adipogenic lineages [24][25][26][27]. Nevertheless, as previously demonstrated by Liao N et al, hADSCs expanded for different passages, showing high mRNA levels of p16, p21 and p53 and an increased ROS production, associated with the appearance of a senescent phenotype.…”

Section: Discussionmentioning

confidence: 99%

Unravelling Cellular Mechanisms of Stem Cell Senescence: An Aid from Natural Bioactive Molecules

Ginesu

et al. 2020

Biology

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Cellular senescence plays a role in the onset of age-related pathologies and in the loss of tissue homeostasis. Natural compounds of food or plants exert an important antioxidant activity, counteracting the formation of harmful free radicals. In the presence of an intense stressing event, cells activate specific responses to counteract senescence or cell death. In the present paper, we aimed at evaluating the levels of expression of specific markers of senescence, in order to demonstrate that extracts from Myrtus Communis L. can prevent premature senescence in ADSCs exposed to oxidative stress. Cells were cultured in the presence of Myrtus extracts for 12–24 and 48 h and then incubated with H2O2 to induce senescence. We then evaluated the expression of senescence-related markers p16, p19, p21, p53, TERT, c-Myc, and the senescence-associated β-Galactoidase activity. Our results showed that pre-treatment with Myrtus extracts protects cells from premature senescence, by regulating the cell cycle, and inducing the expression of TERT and c-Myc. These findings suggest a potential application of these natural compounds in the prevention and treatment of various diseases, counteracting premature senescence and preserving tissue functions.