Mesenchymal Stem Cell Derived Extracellular Vesicles in Aging

Abstract

Aging is associated with high prevalence of chronic degenerative diseases that take a large part of the increasing burden of morbidities in a growing demographic of elderly people. Aging is a complex process that involves cell autonomous and cell nonautonomous mechanisms where senescence plays an important role. Senescence is characterized by the loss of proliferative potential, resistance to cell death by apoptosis and expression of a senescence-associated secretory phenotype (SASP). SASP includes pro-inflammatory cytokines and chemokines, tissue-damaging proteases, growth factors; all contributing to tissue microenvironment alteration and loss of tissue homeostasis. Emerging evidence suggests that the changes in the number and composition of extracellular vesicles (EVs) released by senescent cells contribute to the adverse effects of senescence in aging. In addition, age-related alterations in mesenchymal stem/stromal cells (MSCs) have been associated to dysregulated functions. The loss of functional stem cells necessary to maintain tissue homeostasis likely directly contributes to aging. In this review, we will focus on the characteristics and role of EVs isolated from senescent MSCs, the potential effect of MSC-derived EVs in aging and discuss their therapeutic potential to improve age-related diseases.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Opportunities and Challenges for Clinical Translation

“…Conversely, confluent MSCs produce lower amounts of EVs than proliferating MSCs (Patel et al, 2017). The impact of senescence on the production and functionality of MSC-EVs in different therapeutic applications has recently been reviewed (Boulestreau et al, 2020). EVs from aging MSCs did not exhibit the protective effect of EVs from young MSCs in an acute lung injury model (Huang et al, 2019).…”

“…Importantly, although quality controls for cell production include cell viability and apoptosis rate measurements, they do not assess cell senescence. Yet, EV yield is higher when using senescent cells, and their cargo composition is altered (abnormal levels of some miRNAs) [for review, see Boulestreau et al (2020)]. The proportion of senescent cells in the production batches and their effect on EV content should be taken into account in quality control procedures.…”

Exosome: A New Player in Translational Nanomedicine

“…Recent studies report increasing proliferation induced by younger MSC-derived secretome, probably due to the secretion of rejuvenating growth factors such as GDF11 [190,191]. Interestingly, other studies have suggested that the secretome of senescent MSCs has a biological effect on their microenvironment [103,189,192,193]. This senescence messaging secretome, or senescence-associated secretory phenotype (SASP), probably induces changes in the cellular transcriptional program [194] which, in turn, lead to changes in the number and composition of EVs, thus reflecting the senescent profile of the parent MSCs [192,193,195].…”

“…Interestingly, other studies have suggested that the secretome of senescent MSCs has a biological effect on their microenvironment [103,189,192,193]. This senescence messaging secretome, or senescence-associated secretory phenotype (SASP), probably induces changes in the cellular transcriptional program [194] which, in turn, lead to changes in the number and composition of EVs, thus reflecting the senescent profile of the parent MSCs [192,193,195]. SASPs have also been reported to play an effective role in inducing senescence in immortalized prostate cells [193].…”

Mesenchymal stem cell (MSc) secretome: A possible therapeutic strategy for intensive-care COVID-19 patients

“…Moreover, we have enough scientific evidence that relates aging to the high prevalence of chronic degenerative diseases with increasing morbidity among the elderly [9]. It is well-known that aging is related to cell senescence, which compromises its proliferative potential and leads to the appearance of a specific secretory phenotype, which creates an unfavorable tissue microenvironment.…”