Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles as Natural Nanocarriers: Concise Review

Abstract

Intercellular communication, through direct and indirect cell contact, is mandatory in multicellular organisms. These last years, the microenvironment, and in particular, transfer by extracellular vesicles (EVs), has emerged as a new communication mechanism. Different biological fluids and cell types are common sources of EVs. EVs play different roles, acting as signalosomes, biomarkers, and therapeutic agents. As therapeutic agents, MSC-derived EVs display numerous advantages: they are biocompatible, non-immunogenic, and stable in circulation, and they are able to cross biological barriers. Furthermore, EVs have a great potential for drug delivery. Different EV isolation protocols and loading methods have been tested and compared. Published and ongoing clinical trials, and numerous preclinical studies indicate that EVs are safe and well tolerated. Moreover, the latest studies suggest their applications as nanocarriers. The current review will describe the potential for MSC-derived EVs as drug delivery systems (DDS) in disease treatment, and their advantages. Thereafter, we will outline the different EV isolation methods and loading techniques, and analyze relevant preclinical studies. Finally, we will describe ongoing and published clinical studies. These elements will outline the benefits of MSC-derived EV DDS over several aspects.

Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stromal Cells as an Efficient Nanocarrier to Deliver siRNA or Drug to Pancreatic Cancer Cells

“…Although the results from in vitro and preclinical animal studies have been encouraging, different steps are still needed to increase quality control and procedure standardization. Indeed, different protocols for the purification, quantification and characterization of EVs are still in use [54]. The lack of standardized methods for the isolation and purification of EVs, the limited efficiency of drug encapsulation in EVs, the isolation of EVs contaminated with impurities (cellular debris, nonexosomal vesicles, proteins) and insufficient production yield remain major challenges.…”

Therapeutic strategy of biological macromolecules based natural bioactive compounds of diabetes mellitus and future perspectives: A systematic review

“…About 200 years ago, most medical treatments were herbal. The advent of allopathic drugs in the 1960s led to a gradual drop in the popularity of herbal remedies, particularly in the Western world [ 40 ]. Nonetheless, there has been a resurgence of interest in and popularity of herbal drugs for several causes, containing privileges concerning the efficacy of herbal drugs, shifting user favorites towards natural drugs, the extreme prices and adverse side effects of current drugs, and advancements in herbal drugs brought about by the progress of modern technology [ 41 ].…”

“…Drug delivery systems based on nanotechnology have been investigated to see whether they can circumvent these drawbacks [ [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] ]. Nanostructured drug delivery devices have superior physicochemical and biological features to their microscale counterparts [ [38] , [39] , [40] , [41] , [42] ]. Optically, the former systems are superior; their surface areas, conductivities, and interactions with biological molecules are enhanced ( Fig.…”

Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases

“…As we focused on autoimmune diseases in the current piece, we should emphasize the pathogenesis of the disease, the current status of the patients, the disease status, and the availability of strong support from previous pre-clinical and clinical studies are essential before referring the patients. Fortunately, among different diseases and conditions, clinicians are provided with more valid data from pre-clinical studies ( 360 – 363 ), clinical trials ( 50 , 364 – 366 ), and comprehensive reviews ( 257 , 367 , 368 ) on the efficiency of EVs in the frame of different autoimmune diseases ( 369 ). Although it is inferred from pre-clinical and clinical data that MSC-EVs are safe and efficient ( 51 , 370 ), and great promise is accompanied by their future applications for treating life-threatening autoimmune diseases, this is of particular importance that we avoid generalization and prejudice regarding their overall efficiency.…”