Abstract
Simple SummaryMesenchymal stem cell extracellular vesicles (MSCEVs) obtained from MSCs can have numerous therapeutic applications via regeneration of various body tissues. There are certain approaches by which the therapeutic effect of MSCEVs can be further potentiated. Translation of MSCEVs from the preclinical to clinical level presents several challenges to investigators. Thus, knowledge of isolation, culturing, application, and various challenges faced during clinical applications of MSCEVs are the important aspects highlighted in the present review.Evidence suggests that stem cells exert regenerative potential via the release of extracellular vesicles. Mesenchymal stem cell extracellular vesicles (MSCEVs) offer therapeutic benefits for various pathophysiological ailments by restoring tissues. Facts suggest that MSCEV action can be potentiated by modifying the mesenchymal stem cells culturing methodology and bioengineering EVs. Limited clinical trials of MSCEVs have questioned their superiority, culturing quality, production scale-up and isolation, and administration format. Translation of preclinically successful MSCEVs into a clinical platform requires paying attention to several critical matters, such as the production technique, quantification/characterization, pharmacokinetics/targeting/transfer to the target site, and the safety profile. Keeping these issues as a priority, the present review was designed to highlight the challenges in translating preclinical MSCEV research into clinical platforms and provide evidence for the regenerative potential of MSCEVs in various conditions of the liver, kidney, heart, nervous system, bone, muscle, cartilage, and other organs/tissues.
Highlights
In the present scenario, whole-organ transplantation is considered as a major choice during treatment of end-organ dysfunction
Administration of iPMSCEVs was shown to be safer compared to induced pluripotent mesenchymal stem cells (iPMSCs) [34,35]. Another myocardial ischemia/reperfusion injury (MI) rat model study revealed that combination treatment of rat bone marrow mesenchymal stem cells (BMMSCs) and derived BMMSCEVs improved cardiac functioning, reduced infarct size, and increased neo-vascularization compared to individual treatment with BMMSCs or BMMSCEVs [36]
Limited clinical studies are available on the enhancement of the beneficial effects of Mesenchymal stem cell extracellular vesicles (MSCEVs) along with bio-engineering and genetic modification, nanomaterials, and drug encapsulation
Summary
Whole-organ transplantation is considered as a major choice during treatment of end-organ dysfunction. Isolation of MSCs can be done from various parts of the human body, such as blood, bone marrow, liver, umbilical cord, periodontal ligament, lung, and adipose tissue [5] Despite their high regenerative potential, MSCs have been challenged in various aspects, such as clinical utility, scale-up, administration, variability, ethics, and safety [6,7,8]. MSCEVs approved at the preclinical level before entering the clinical phase face many challenges, such as production technique, quantification/characterization, pharmacokinetics/targeting/transfer, and safety profile [16] Acknowledging these issues as major concerns, the current review presents the challenges of translating preclinical MSCEVs to the clinical level and the latest regenerative potential of MSCEVs in tissue engineering of various organs
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