Abstract
Mesenchymal stem cells (MSCs) are being extensively investigated for their potential in tissue engineering and regenerative medicine. However, recent evidence suggests that the beneficial effects of MSCs may be manifest by their released extracellular vesicles (EVs); typically not requiring the administration of MSCs. This evidence, predominantly from pre-clinical in vitro and in vivo studies, suggests that MSC-EVs may exhibit substantial therapeutic properties in many pathophysiological conditions, potentially restoring an extensive range of damaged or diseased tissues and organs. These benefits of MSC EVs are apparently found, regardless of the anatomical or body fluid origin of the MSCs (and include e.g., bone marrow, adipose tissue, umbilical cord, urine, etc). Furthermore, early indications suggest that the favourable effects of MSC-EVs could be further enhanced by modifying the way in which the donor MSCs are cultured (for example, in hypoxic compared to normoxic conditions, in 3D compared to 2D culture formats) and/or if the EVs are subsequently bio-engineered (for example, loaded with specific cargo). So far, few human clinical trials of MSC-EVs have been conducted and questions remain unanswered on whether the heterogeneous population of EVs is beneficial or some specific sub-populations, how best we can culture and scale-up MSC-EV production and isolation for clinical utility, and in what format they should be administered. However, as reviewed here, there is now substantial evidence supporting the use of MSC-EVs in tissue engineering and regenerative medicine and further research to establish how best to exploit this approach for societal and economic benefit is warranted.
Highlights
For some patients with end-organ dysfunction, whole organ transplantation is an established treatment option [1]
Many studies have reported miRNA within extracellular vehicles (EVs) being transferred to recipient cells and subsequently altering the gene expression and phenotype of those cells e.g., modulating cycle, apoptosis, migration, inflammation, and neo-angiogenesis [35,36,37,38]. While these studies related to EV biogenesis and characterisation are not all focussed on mesenchymal stem cells (MSCs), it seems that MSC-EVs are heterogeneous, carry cargo such as proteins, nucleic acids and lipids, and are involved in cell-to-cell communication
A world-wide survey by the International Society for Extracellular Vesicles (ISEV) [39], considering EV isolation from any and all sourced showed ultracentrifugation-based methods to be most commonly used, a range of other approaches have been taken to overcome challenges regarding ultracentrifugation including the need for an ultracentrifuge, low-throughput of samples, and potential damage to EVs caused by high-speed centrifugation [40,41]
Summary
For some patients with end-organ dysfunction, whole organ transplantation is an established treatment option [1]. In light of their multiple sources as well as therapeutic versatility, mesenchymal stem cells (MSCs) have been proposed as the most appropriate cell source for these applications [4,5]. As stem cells, they exhibit beneficial characteristics as compared to terminally differentiated cells, including the potential to circumvent immuno-reaction in vitro and in vivo and to differentiate towards a broad range of specific. EVs are heterogeneous lipid bilayer-surrounded vesicles secreted by all cell types, MSCs, are heterogeneous lipid bilayer-surrounded vesicles cell types,physiological and act asEVs mediators of intercellular communication.
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