Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells

Mato-Basalo, Rocío; Morente-López, Miriam; Arntz, Onno J.; Loo, Fons A. J. van de; Fafián-Labora, Juan; Arufe, M.C.

doi:10.3390/ijms22073367

Cited by 25 publications

(24 citation statements)

References 40 publications

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“…It has been reported that TA-MSC treatment of healthy donors with 20 ng/mL of TNF-α for 24 h induces SASP with increased expression of IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) [172]. Even UC-MSCs treated with 5 ng/mL of TNF-α for three days have been used as a model of senescence [177]. This indicates the need to analyze in detail the effect of cytokine concentrations and exposure times on MSC functions.…”

Section: Alterations In Cell Morphology and Proliferationmentioning

confidence: 99%

TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

López-García

Castro-Manrreza

2021

IJMS

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Mesenchymal stem/stromal cells (MSCs) have an immunoregulatory capacity and have been used in different clinical protocols requiring control of the immune response. However, variable results have been obtained, mainly due to the effect of the microenvironment on the induction, increase, and maintenance of MSC immunoregulatory mechanisms. In addition, the importance of cell–cell contact for MSCs to efficiently modulate the immune response has recently been highlighted. Because these interactions would be difficult to achieve in the physiological context, the release of extracellular vesicles (EVs) and their participation as intermediaries of communication between MSCs and immune cells becomes relevant. Therefore, this article focuses on analyzing immunoregulatory mechanisms mediated by cell contact, highlighting the importance of intercellular adhesion molecule-1 (ICAM-1) and the participation of EVs. Moreover, the effects of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), the main cytokines involved in MSC activation, are examined. These cytokines, when used at the appropriate concentrations and times, would promote increases in the expression of immunoregulatory molecules in the cell and allow the acquisition of EVs enriched with these molecules. The establishment of certain in vitro activation guidelines will facilitate the design of conditioning protocols to obtain functional MSCs or EVs in different pathophysiological conditions.

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Section: Alterations In Cell Morphology and Proliferationmentioning

confidence: 99%

TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

López-García

Castro-Manrreza

2021

IJMS

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“…the downstream interferon signaling molecule IFITM3, which is located on the EV membrane and enriched during senescence (96). Induction of senescence by EVs may also depend on activation of NF-κ B in recipient cells (97). Furthermore, a deficiency in SIRT1 activity, which is decreased in multiple tissues during aging (98) and regulates longevity (71), can induce secretion of EVs or endothelial microparticles (56,99,100).…”

Section: Accepted Articlementioning

confidence: 99%

Friends and foes: Extracellular vesicles in aging and rejuvenation

Lananna

Imai

2021

FASEB BioAdvances

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Extracellular vesicles (EVs) are released by many different cell types throughout the body and play a role in a diverse range of biological processes. EVs circulating in blood as well as in other body fluids undergo dramatic alterations over an organism's lifespan that are only beginning to be elucidated. The exact nature of these changes is an area of active and intense investigation, but lacks clear consensus due to the substantial heterogeneity in EV subpopulations and insufficiencies in current technologies. Nonetheless, emerging evidence suggests that EVs regulate systemic aging as well as the pathophysiology of age-related diseases. Here, we review the current literature investigating EVs and aging with an emphasis on consequences for the maintenance of human healthspan. Intriguingly, the biological utility of EVs both in vitro and in vivo and across contexts depends on the states of the source cells or tissues. As such, EVs secreted by cells in an aged or pathological state may impose detrimental consequences on recipient cells, while EVs secreted by youthful or healthy cells may promote functional improvement. Thus, it is critical to understand both functions of EVs and tip the balance towards their beneficial effects as an anti-aging intervention. Accepted ArticleNo copyright is required Biogenesis of small versus large EVs occurs via divergent pathways that nonetheless involve some of the same regulatory molecules. Small EVs are generated by a secondary invagination of the luminal membrane of endosomes following endocytosis, forming multivesicular bodies (MVBs).These MVBs then fuse with the cellular outer plasma membrane, emptying their contents including the nascent small EVs into the extracellular space. In contrast, large EVs form by directly budding from the external cellular plasma membrane (15). Description of current knowledge regarding the biogenesis, uptake, and basic biological functions of EVs are beyond the scope of this review, but are reviewed in detail elsewhere (5,15). Importantly, EVs can serve as both local and long-range transport and intertissue signaling mechanisms for mRNA, miRNA, protein, and lipids and are a major source for cell-free DNA and RNA in humans (15)(16)(17)(18)(19)(20). In this review article, we will focus on the biological significance of EVs in the systemic regulation of mammalian aging and longevity and also in the pathogenesis of age-associated dysfunctions. II. Changes to extracellular vesicles with ageEV quantification: Recent evidence suggests that there are substantial changes to EVs with age.Nevertheless, the extent of these changes and whether they represent a cause or effect of aging remain largely unanswered questions in the field. Such changes could be viewed as potential boons to our understanding of the aging process as well as in our search for viable aging biomarkers in humans. Analysis of plasma from 74 humans including young (30-35 years old), middle-aged (40-55 years old), and old (55-64 years old) revealed gradually decreasing quantities of circu...

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“…To optimize the clinical applications, the approaches used to develop biological products based on the molecular properties of MSCs and their mechanisms of action are being studied. Among these approaches, the paracrine function of MSCs via the secretome, which involves conditioned media (CM), EVs, and exosomes, is considered to be representative [ 5 , 9 , 13 , 14 , 15 , 16 , 17 ]. The CM derived from BM-MSCs and MB-MSCs have been shown to be capable of stimulating tube-like formation of human umbilical vein endothelial cells [ 5 ].…”

mentioning

confidence: 99%

“…In addition, the capacity to inhibit inflammation, which is consistent with the main actions described for EVs in general [ 15 , 18 ], has been observed in animal BPD models. Transmission of cellular senescence and proinflammatory activation between MSCs and their EVs are involved in the development of inflamm-aging, which is associated with the degeneration of organs and tissues during aging [ 16 ]. Mato-Basalo et al reported that treatment of senescent UC-MSCs with small inhibitors (e.g., JSH-23, MG-132, or curcumin) prevented cellular senescence and proinflammatory activation in MSCs, and paracrine and proinflammatory transmission by EVs through inhibition of the p65 pathway [ 16 ].…”

mentioning

confidence: 99%

“…To advance the development of innovative stem cell therapies, priming [ 15 , 16 , 17 , 18 , 19 ] or genetic engineering of MSCs and biomaterial-based physical/structural modification [ 5 , 13 , 15 ] of MSCs have been studied. Treatment of AD-MSCs with fibronectin-derived peptide has been shown to improve their proliferation and differentiation into osteoblasts [ 19 ].…”

mentioning

confidence: 99%

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