Isabelle Grenier-Pleau

Bio: Isabelle Grenier-Pleau is an academic researcher from Queen's University. The author has contributed to research in topics: Haematopoiesis & Vesicle. The author has an hindex of 1, co-authored 2 publications receiving 5 citations.

Blood extracellular vesicles from healthy individuals regulate hematopoietic stem cells as humans age

Abstract: Hematopoietic stem cells (HSCs) maintain balanced blood cell production in a process called hematopoiesis. As humans age, their HSCs acquire mutations that allow some HSCs to disproportionately contribute to normal blood production. This process, known as age-related clonal hematopoiesis, predisposes certain individuals to cancer, cardiovascular and pulmonary pathologies. There is a growing body of evidence suggesting that factors outside cells, such as extracellular vesicles (EVs), contribute to the disruption of stem cell homeostasis during aging. We have characterized blood EVs from humans and determined that they are remarkably consistent with respect to size, concentration, and total protein content, across healthy subjects aged 20-85 years. When analyzing EV protein composition from mass spectroscopy data, our machine-learning-based algorithms are able to distinguish EV proteins based on age and suggest that different cell types dominantly produce EVs released into the blood, which change over time. Importantly, our data show blood EVs from middle and older age groups (>40 years) significantly stimulate HSCs in contrast to untreated and EVs sourced from young subjects. Our study establishes for the first time that although EV particle size, concentration, and total protein content remain relatively consistent over an adult lifespan in humans, EV content evolves during aging and potentially influences HSC regulation.

Ageing and rejuvenation of tissue stem cells and their niches

Abstract: Most adult organs contain regenerative stem cells, often organized in specific niches. Stem cell function is critical for tissue homeostasis and repair upon injury, and it is dependent on interactions with the niche. During ageing, stem cells decline in their regenerative potential and ability to give rise to differentiated cells in the tissue, which is associated with a deterioration of tissue integrity and health. Ageing-associated changes in regenerative tissue regions include defects in maintenance of stem cell quiescence, differentiation ability and bias, clonal expansion and infiltration of immune cells in the niche. In this Review, we discuss cellular and molecular mechanisms underlying ageing in the regenerative regions of different tissues as well as potential rejuvenation strategies. We focus primarily on brain, muscle and blood tissues, but also provide examples from other tissues, such as skin and intestine. We describe the complex interactions between different cell types, non-cell-autonomous mechanisms between ageing niches and stem cells, and the influence of systemic factors. We also compare different interventions for the rejuvenation of old regenerative regions. Future outlooks in the field of stem cell ageing are discussed, including strategies to counter ageing and age-dependent disease. Stem cell function declines during ageing, resulting in the loss of tissue integrity and health deterioration. Ageing is associated with defects in the maintenance of stem cell quiescence and cell differentiation ability, clonal expansion and infiltration of immune cells in the niche. This Review discusses the mechanisms underlying ageing in stem cells and their niches, and potential rejuvenation strategies.

Influences of age, race, and sex on extracellular vesicle characteristics

Abstract: Recent attention has focused on the use of extracellular vesicles (EVs) as biological indicators of health and disease. These small, nano-sized membrane bound vesicles are secreted from cells into the extracellular space and can be readily isolated from bodily fluids. EVs can carry various bioactive molecules as cargo including DNA, RNA, proteins, and lipids. These EVs can provide a snapshot of the cell of origin and a window of opportunity to assess normal physiological states as well as pathophysiological states. For EVs to further develop as potential biomarkers of disease, it is important to characterize whether these vesicles and their associated cargo are altered in the context of demographic factors. Here, we summarize the current literature on how demographics such as age, race, and sex affect the levels and cargo of EVs. Age and sex influence both EV cargo and concentration while race studies report differences mostly in EV protein cargo. This review also identifies areas of future research and important considerations for the clinical use of EVs as biomarkers.

Cell and Cell-Free Therapies to Counteract Human Premature and Physiological Aging: MSCs Come to Light.

Abstract: The progressive loss of the regenerative potential of tissues is one of the most obvious consequences of aging, driven by altered intercellular communication, cell senescence and niche-specific stem cell exhaustion, among other drivers. Mesenchymal tissues, such as bone, cartilage and fat, which originate from mesenchymal stem cell (MSC) differentiation, are especially affected by aging. Senescent MSCs show limited proliferative capacity and impairment in key defining features: their multipotent differentiation and secretory abilities, leading to diminished function and deleterious consequences for tissue homeostasis. In the past few years, several interventions to improve human healthspan by counteracting the cellular and molecular consequences of aging have moved closer to the clinic. Taking into account the MSC exhaustion occurring in aging, advanced therapies based on the potential use of young allogeneic MSCs and derivatives, such as extracellular vesicles (EVs), are gaining attention. Based on encouraging pre-clinical and clinical data, this review assesses the strong potential of MSC-based (cell and cell-free) therapies to counteract age-related consequences in both physiological and premature aging scenarios. We also discuss the mechanisms of action of these therapies and the possibility of enhancing their clinical potential by exposing MSCs to niche-relevant signals.

Exercise, healthy ageing, and the potential role of small extracellular vesicles

Abstract: Extracellular vesicles (EVs) can be released from most cells in the body and act as intercellular messengers transferring information in their cargo to affect cellular function. A growing body of evidence suggests that a subset of EVs, referred to here as 'small extracellular vesicles' (sEVs), can accelerate or slow the processes of ageing and age-related diseases dependent on their molecular cargo and cellular origin. Continued exploration of the vast complexity of the sEV cargo aims to further characterise these systemic vehicles that may be targeted to ameliorate age-related pathologies. Marked progress in the development of mass spectrometry-based technologies means that it is now possible to characterise a significant proportion of the proteome of sEVs (surface and cargo) via unbiased proteomics. This information is vital for identifying biomarkers and the development of sEV-based therapeutics in the context of ageing. Although exercise and physical activity are prominent features in maintaining health in advancing years, the mechanisms responsible are unclear. A potential mechanism by which plasma sEVs released during exercise could influence ageing and senescence is via the increased delivery of cargo proteins that function as antioxidant enzymes or inhibitors of senescence. These have been observed to increase in sEVs following acute and chronic exercise, as identified via independent interrogation of high coverage, publicly available proteomic datasets. Establishing tropism and exchange of functionally active proteins by these processes represents a promising line of enquiry in implicating sEVs as biologically relevant mediators of the ageing process.

An Isolation System to Collect High Quality and Purity Extracellular Vesicles from Serum.

Abstract: Purpose Extracellular vesicles (EVs) are membrane-encapsulated nanoparticles that function as carriers and play a role in intercellular communication There are a large number of EVs in the blood and serve as an indicator of pathophysiological conditions Studies on the basics and application of EVs are hampered by the limitations of current protocols to isolate EVs from blood However, current isolation methods are difficult to achieve a balance between yield and purity Methods Firstly, we use Sepharose-4B to build a self-made size exclusion chromatography (SEC) column and perform separation and characteristics Then, we use the SEC column to systematically compare the efficiency with the most common EV isolation methods: Ultracentrifugation (UC) and total exosomes isolation commercial kit (TEI) The EVs isolated through different methods were characterized the yield and size of EVs, analyzed their protein profiles, the morphology and purity were observed under the transmission electron microscope To further improve the quality and purity, we combined SEC and UC methods and established a two-steps method to isolated EVs from serum Results Self-made SEC column can well separate EVs from complex serum protein, and EVs enriched in the 8-13 fractions with good morphology and yield By systematically compare SEC with the commonly used UC and TEI kit, SEC is outstanding in all aspects and balances both isolation purity and yield However, using the SEC method alone still has certain limitations and residual impurities The SEC+UC combined method can cleverly solve the shortcomings of SEC and optimize the quality and purity of EVs from serum, which is much better than using one method alone Conclusion Our study presents the combination of size-exclusion chromatography and ultracentrifugation as a feasible and time-saving method to isolate high-quality and purity extracellular vesicles from serum