Effect of Melatonin for Regulating Mesenchymal Stromal Cells and Derived Extracellular Vesicles.
TL;DR: The role of melatonin in regulating mesenchymal stromal cells (MSCs) via paracrine signaling has been discussed in this article, where the synthesis of the pineal gland is discussed.
Abstract: Melatonin is a hormone, synthesized in the pineal gland, which primarily controls the circadian rhythm of the body. In recent years, melatonin has also been shown to regulate metabolism, provide neuroprotection, and act as an anti-inflammatory, free radical scavenger. There has also been a recent research interest in the role of melatonin in regulating mesenchymal stromal cells (MSCs). MSCs are pivotal for their ability to differentiate into a variety of different tissues. There is also increasing evidence for the therapeutic prospects of MSCs via paracrine signaling. In addition to secreting cytokines and chemokines, MSCs can secrete extracellular vesicles (EVs), allowing them to respond to injury and promote tissue regeneration. While there has been a major research interest in the use of MSCs for regenerative medicine, the clinical application is limited by many risks, including tumorigenicity, senescence, and sensitivity to toxic environments. The use of MSC-derived EVs for cell-free therapy can potentially avoid the disadvantages of MSCs, which makes this an exciting prospect for regenerative medicine. Prior research has shown that MSCs, via paracrine mechanisms, can identify receptor-independent responses to melatonin and then activate a series of downstream pathways, which exert a variety of effects, including anti-tumor and anti-inflammatory effects. Here we review the synthesis of melatonin, its mechanisms of action, and the effect of melatonin on MSCs via paracrine signaling. Furthermore, we summarize the current clinical applications of melatonin and discuss future prospects.
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TL;DR: In this article , the authors evaluated the activity of melatonin in modulating HSPC senescence, in the attempt to improve their hemopoietic regenerative potential.
3 citations
TL;DR: In this paper , the relationship between the circadian clock and mesenchymal stem cell fate decisions in the skeletal system was investigated and shown to be a promising candidate for health improvement and disease prevention.
Abstract: The circadian clock refers to the intrinsic biological rhythms of physiological functions and behaviours. It synergises with the solar cycle and has profound effects on normal metabolism and organismal fitness. Recent studies have suggested that the circadian clock exerts great influence on the differentiation of stem cells. Here, we focus on the close relationship between the circadian clock and mesenchymal stem cell fate decisions in the skeletal system. The underlying mechanisms include hormone signals and the activation and repression of different transcription factors under circadian regulation. Additionally, the clock interacts with epigenetic modifiers and non-coding RNAs and is even involved in chromatin remodelling. Although the specificity and safety of circadian therapy need to be further studied, the circadian regulation of stem cells can be regarded as a promising candidate for health improvement and disease prevention.
2 citations
TL;DR: In this article , the relationship between the circadian clock and mesenchymal stem cell fate decisions in the skeletal system was investigated and shown to be a promising candidate for health improvement and disease prevention.
Abstract: The circadian clock refers to the intrinsic biological rhythms of physiological functions and behaviours. It synergises with the solar cycle and has profound effects on normal metabolism and organismal fitness. Recent studies have suggested that the circadian clock exerts great influence on the differentiation of stem cells. Here, we focus on the close relationship between the circadian clock and mesenchymal stem cell fate decisions in the skeletal system. The underlying mechanisms include hormone signals and the activation and repression of different transcription factors under circadian regulation. Additionally, the clock interacts with epigenetic modifiers and non-coding RNAs and is even involved in chromatin remodelling. Although the specificity and safety of circadian therapy need to be further studied, the circadian regulation of stem cells can be regarded as a promising candidate for health improvement and disease prevention.
2 citations
TL;DR: In this paper , a review of the regulatory mechanisms of melatonin in osteoblastic differentiation of mesenchymal stem cells and underling involved signaling pathways as well as the clinical potential of using Melatonin in bone degenerative disorders is presented.
1 citations
01 Jan 2023
TL;DR: In this article , the main risk elements of aging, antioxidant properties, and action of MLT, as well as MLT achievement in the pathogenesis of neurodegenerative diseases and its associations with the nine biological hallmarks of aging are discussed.
Abstract: AbstractMammalian cells have multifaceted systems and structures to avoid accumulation of unfolded or misfolded proteins, the accumulation of which is a feature of aging and aging-related conditions. With a gradually increasing elderly population, aging-related pathologies such as neurodegenerative disorders, cancer, and cardiovascular diseases are becoming a growing economic, social, and personal problem. Few or no effective treatments are presented for aging-associated neurodegenerative conditions, which progress in an irreversible way.Melatonin (MLT), a pineal hormone and an endogenous antioxidant, has numerous physiological functions in the brain, including regulating circadian rhythms, scavenging free radicals, preventing oxidation, and suppressing neuroinflammation. Clinical studies revealed that MLT levels are significantly reduced in patients with neurodegenerative diseases. Research proved that MLT prevents activity on neurodegeneration. As a chronobiotic, MLT can modify circadian rhythm. As a cytoprotective molecule, it prevents inflammatory injury in neurodegenerative diseases and aging.This chapter discusses neurodegenerative diseases, which are the main risk elements of aging, antioxidant properties, and action of MLT, as well as MLT achievement in the pathogenesis of neurodegenerative diseases and its associations with the nine biological hallmarks of aging. The main physiological mechanisms of aging and their potential as targets of novel treatments for neurodegenerative diseases are also discussed.KeywordsMelatoninAgingOxidative stressNeurodegenerative diseasesCancer
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Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4 +414 more•Institutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
5,988 citations
TL;DR: In this paper, the authors assess recent research in this field, argue for a restricted definition, and explore pathways by which the T helper 2 (Th2) cell cytokines interleukin-4 (IL-4) and IL-13 mediate their effects on macrophage cell biology, their biosynthesis, and responses to a normal and pathological microenvironment.
3,450 citations
TL;DR: Recent progress in understanding extracellular vesicle biology and the role of extrace cellular vesicles in disease is reviewed, emerging therapeutic opportunities are discussed and the associated challenges are considered.
Abstract: Within the past decade, extracellular vesicles have emerged as important mediators of intercellular communication, being involved in the transmission of biological signals between cells in both prokaryotes and higher eukaryotes to regulate a diverse range of biological processes. In addition, pathophysiological roles for extracellular vesicles are beginning to be recognized in diseases including cancer, infectious diseases and neurodegenerative disorders, highlighting potential novel targets for therapeutic intervention. Moreover, both unmodified and engineered extracellular vesicles are likely to have applications in macromolecular drug delivery. Here, we review recent progress in understanding extracellular vesicle biology and the role of extracellular vesicles in disease, discuss emerging therapeutic opportunities and consider the associated challenges.
2,507 citations
TL;DR: The linear increase in the number of colonies with increasing numbers of explanted cells and the distribution of male and female cells in mixed cultures support the view that fibroblast colonies are clones.
Abstract: In monolayer cultures of guinea-pig bone marrow and spleen the development of discrete fibroblast colonies takes place on days 9–12. The linear increase in the number of colonies with increasing numbers of explanted cells and the distribution of male and female cells in mixed cultures support the view that fibroblast colonies are clones. The concentration of colony-forming cells in bone marrow and spleen is approximately 10-5. Bone marrow culture (but not spleen culture) fibroblasts are capable of spontaneous bone formation in diffusion chambers. Fibroblasts from both bone marrow and spleen cultures are inducible to osteogenesis in diffusion chambers in the presence of transitional epithelium.
2,482 citations
TL;DR: The novel role of exosomes highlights a new perspective into intercellular mediation of tissue injury and repair, and engenders novel approaches to the development of biologics for tissue repair.
1,816 citations