0000000000222487
AUTHOR
Jorge Sanz-ros
Influence of partial O 2 pressure on the adhesion, proliferation, and osteogenic differentiation of human dental pulp stem cells on β-tricalcium phosphate scaffold
Our purpose was to analyse the influence of O2 pressure on the adhesion, proliferation, and osteogenic differentiation of human dental pulp stem cells (DPSC) on 3-tricalcium phosphate (3-TCP) scaffold. DPSC isolated from extracted third molars were seeded on 3-TCP and cultured under 3% or 21% O2 pressure. Cell adhesion, proliferation, and differentiation over the biomaterial were evaluated at 7, 13, 18, and 23 days of culture. Cell adhesion was determined by light microscopy, proliferation by DNA quantification, and osteogenic differentiation by alkaline phosphatase activity analysis. All DPSC adhered to 3-TCP with both O2 conditions. Cell proliferation values were higher at 3% O2 in each t…
Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine
The key hallmark of stem cells is their ability to self-renew while keeping a differentiation potential. Intrinsic and extrinsic cell factors may contribute to a decline in these stem cell properties, and this is of the most importance when culturing them. One of these factors is oxygen concentration, which has been closely linked to the maintenance of stemness. The widely used environmental 21% O2 concentration represents a hyperoxic non-physiological condition, which can impair stem cell behaviour by many mechanisms. The goal of this review is to understand these mechanisms underlying the oxygen signalling pathways and their negatively-associated consequences. This may provide a rationale…
Centenarian offspring: A model for understanding healthy aging
Centenarians exhibit extreme longevity showing a compression of morbidity. We showed previously that microRNA expression profiles and plasma protein carbonylation in centenarians and young people are similar, whereas they are very different from that found in old individuals. This suggests that centenarians have a better control of homeostasis and are protected against oxidative damage. In this study, we aimed to determine if such characteristic microRNA expression profile and lower protein oxidation status in centenarians may be inherited by their offspring. For this purpose, we collected plasma and peripheral blood mononuclear cells from 90 septuagenarians, 68 centenarians and 46 centenar…
Antioxidant role of microvesicles, activated by genistein, in stem cells
Intercellular communication is an essential hallmark of multicellular organisms. Microvesicles (MVs), which are released from and taken up by most types of cells are involved in intercellular communication. The nutrients we ingest from food contact with immune cells in the bloodstream and can promote the formation of MVs. Some foods contain molecules with regulatory activity, such as genistein, a polyphenol found in soy. We aimed to study the effects of MVs released from genistein-treated immune cells on dental pulp stem cells (DPSC). We obtained peripheral blood mononuclear cells (PBMC) from 5 young women (aged 18–25). Cells were cultured and treated with 0.5 μM genistein or 0.01% DMSO as …
Small extracellular vesicles from young mice prevent frailty, improve healthspan and decrease epigenetic age in old mice
SummaryAging is associated with an increased risk of frailty, disability, comorbidities, institutionalization, falls, fractures, hospitalization, and mortality. Searching for strategies to delay the degenerative changes associated with aging and frailty is interesting. We treated old animals intravenously with small extracellular vesicles (sEVs) derived from adipose mesenchymal stem cells (ADSCs) of young animals, and we found an improvement of several functional parameters usually altered with aging, such as motor coordination, grip strength, fatigue resistance, fur regeneration, and renal function. Frailty index analysis showed that 40% of old control mice were frail, whereas none of the …
Extracellular Vesicles from Healthy Cells Improves Cell Function and Stemness in Premature Senescent Stem Cells by miR-302b and HIF-1α Activation.
Aging is accompanied by the accumulation of senescent cells that alter intercellular communication, thereby impairing tissue homeostasis and reducing organ regenerative potential. Recently, the administration of mesenchymal stem cells (MSC)-derived extracellular vesicles has proven to be more effective and less challenging than current stem cell-based therapies. Extracellular vesicles (EVs) contain a cell-specific cargo of proteins, lipids and nucleic acids that are released and taken up by probably all cell types, thereby inducing functional changes via the horizontal transfer of their cargo. Here, we describe the beneficial properties of extracellular vesicles derived from non-senescent M…
Therapeutic Potential of Extracellular Vesicles in Aging and Age-Related Diseases
Aging is associated with an alteration of intercellular communication. These changes in the extracellular environment contribute to the aging phenotype and have been linked to different aging-related diseases. Extracellular vesicles (EVs) are factors that mediate the transmission of signaling molecules between cells. In the aging field, these EVs have been shown to regulate important aging processes, such as oxidative stress or senescence, both in vivo and in vitro. EVs from healthy cells, particularly those coming from stem cells (SCs), have been described as potential effectors of the regenerative potential of SCs. Many studies with different animal models have shown promising results in …
Relationship between diet, microbiota, and healthy aging
Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/2227-9059/8/8/287 Este artículo pertenece al número especial "Oxidative stress and inflammation: from mechanisms to therapeutic approaches". En este artículo también participan: Marta Inglés, Gloria Olaso, Juan Gambini y Cristina Mas-Bargues. Due to medical advances and lifestyle changes, population life expectancy has increased. For this reason, it is important to achieve healthy aging by reducing the risk factors causing damage and pathologies associated with age. Through nutrition, one of the pillars of health, we are able to modify these factors through modulation of the intestinal microbiota. The Mediterran…
Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells
Human dental pulp stem cells (hDPSCs) are a source for cell therapy. Before implantation, an in vitro expansion step is necessary, with the inconvenience that hDPSCs undergo senescence following a certain number of passages, loosing their stemness properties. Long-term in vitro culture of hDPSCs at 21% (ambient oxygen tension) compared with 3–6% oxygen tension (physiological oxygen tension) caused an oxidative stress-related premature senescence, as evidenced by increased β-galactosidase activity and increased lysil oxidase expression, which is mediated by p16INK4a pathway. Furthermore, hDPSCs cultured at 21% oxygen tension underwent a downregulation of OCT4, SOX2, KLF4 and c-MYC factors, w…
Drosophila melanogaster overexpression FAS live longer
FAS and FAS ligand is critical in the control of the extension of extrinsic pathway of apoptosis. In previous studies we have performed transcriptomics peripheral blood cells from centenarians, octogenarians and young persons and we found over expression in centenarians of the FAS receptor. To confirm the role of FAS ligand in longevity across animal species, we have generated Drosophila melanogaster that over expresses this gene using the GAL4-UAS technique. The results show that flies overexpressing FAS increase maximal longevity in twelve percent and average longevity in six percent. Therefore, we confirm that FAS is related to longevity flight.
Extracellular vesicles and redox modulation in aging
Extracellular vesicles (EVs) are nowadays known to be mediators of cell-to-cell communication involved in physiological and pathological processes. The current expectation is their use as specific biomarkers and therapeutic tools due to their inner characteristics. However, several investigations still need to be done before we can use them in the clinic. First, their categorization is still under debate, although an accurate classification of EVs subtypes should be based on physical characteristics, biochemical composition or condition description of the cell of origin. Second, EVs carry lipids, proteins and nucleic acids that can induce epigenetic modifications on target cells. These carg…
Alzheimer's disease: Only prevention makes sense
Alzheimer's disease therapeutics is one of the most important endeavours in today's clinical investigation. Over more than 30 years of research, no disease-modifying treatment has been approved by either the FDA or the EMA to treat Alzheimer's disease. Recently, the evidence of pathological alterations in the brain tissue has been gathered showing that the signs of brain damage appear more than 20 years before the onset of Alzheimer's dementia. The major aim of this review is to underpin the idea that in Alzheimer's therapeutics, only prevention makes sense. It is difficult to visualise that would-be patients may be treated with endovenous administration of antibodies for several years to d…
The Relationship between Diet and Frailty in Aging
The increase in lifespan in the 20th century entails an increase in the elderly population. This brings a new challenge for society, causing people to have physical and mental limitations caused by age-related diseases, such as frailty. Frailty is clinically characterized by multisystem pathophysiological processes, such as chronic inflammation, immune activation, dysregulation of the musculoskeletal and endocrine systems, oxidative stress, energy imbalances, mitochondrial dysfunction, and sarcopenia. The elderly should consume energy in amounts close to those in what is currently accepted as a balanced diet. However, an increase in protein intake may be recommended for elderly people as l…
BCL-xL, a Mitochondrial Protein Involved in Successful Aging: From C. elegans to Human Centenarians
B-Cell Lymphoma-extra-large (BCL-xL) is involved in longevity and successful aging, which indicates a role for BCL-xL in cell survival pathway regulation. Beyond its well described role as an inhibitor of apoptosis by preventing cytochrome c release, BCL-xL has also been related, indirectly, to autophagy and senescence pathways. Although in these latter cases, BCL-xL has dual roles, either activating or inhibiting, depending on the cell type and the specific conditions. Taken together, all these findings suggest a precise mechanism of action for BCL-xL, able to regulate the crosstalk between apoptosis, autophagy, and senescence, thus promoting cell survival or cell death. All three pathways…
Centenarians: An excellent example of resilience for successful ageing.
Centenarians are remarkable not only because of their prolonged life, but also because they compress morbidity until the very last moments of their lives, thus being proposed as a model of successful, extraordinary ageing. From the medical viewpoint, centenarians do not escape the physiological decline or the age-related diseases or syndromes (i.e. frailty), but the rate of such processes is slow enough to be counterbalanced by their increased intrinsic capacity to respond to minor stresses of daily life (i.e. resilience). These new concepts are reviewed in this paper. Allostatic stresses lead to a chronic low-grade inflammation that has led to the proposal of the "inflammaging" theory of a…
Small extracellular vesicles from young adipose-derived stem cells prevent frailty, improve health span, and decrease epigenetic age in old mice.
Aging is associated with an increased risk of frailty, disability, and mortality. Strategies to delay the degenerative changes associated with aging and frailty are particularly interesting. We treated old animals with small extracellular vesicles (sEVs) derived from adipose mesenchymal stem cells (ADSCs) of young animals, and we found an improvement in several parameters usually altered with aging, such as motor coordination, grip strength, fatigue resistance, fur regeneration, and renal function, as well as an important decrease in frailty. ADSC-sEVs induced proregenerative effects and a decrease in oxidative stress, inflammation, and senescence markers in muscle and kidney. Moreover, pre…