Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications

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.

Human Adipose Tissue-Derived Stromal Cells Suppress Human, but Not Murine Lymphocyte Proliferation, via Indoleamine 2,3-Dioxygenase Activity

“…With increasing knowledge, it became evident that some of the regulatory activities relate to soluble factors and thus are found in MSC-CM and EV [14]. EV anti-apoptotic, angiogenic and regenerative potentials have made them rise as a potential alternative cell-free therapeutic prospect circumventing many of the safety challenges regarded in cell therapy [15]. EV, small vesicles secreted by a variety of cell types, are known to take part in cell-cell communication [16].…”

COVID-19 and Extracellular Vesicles: An Intriguing Interplay

“…Preliminary studies suggest that EVs isolated from the cell secretome might also be efficient for the treatment of COVID-19 [20]. MSC-derived EVs were shown to produce similar effects as their parent cells; and they can be safely stored for long periods without losing function and have shown similar or better results than MSCs in animal models [19].…”

“…Coronavirus disease 2019 (COVID- 19) will have a long-lasting impact on the biopharmaceutical industry. In particular, the urgent need both for a preventive vaccine and for advanced therapeutics will stimulate the growth of the post-COVID-19 bioindustry in ways that were unthinkable before.…”

Conditioned Medium of Bone Marrow Mesenchymal Stem Cells Relieves Acute Lung Injury in Mice by Regulating Epithelial Sodium Channels via miR-34c

“…Of note, BMSCs have many advantages, such as extensive sources, easy to culture in vitro, and less ethical issues, so the study of BMSCs is more extensive at present. Researchers have reported that MSCs can exert beneficial effects by their released extracellular vesicles, however, whether ENaC is involved in the above process is still rarely known [30]. It has been confirmed that patients with ALI have disorders of pulmonary fluid clearance, and evidence has also shown that reabsorption of Na + by ENaC is an important step to maintain the balance of alveolar fluid [31].…”