TABLE 1.

Possible challenges and required criteria related to clinical application of EVs.

Criteria	Challenges
Isolation and purification techniques	Isolated the contamination EVs with virions and other infectious particles different isolation and purification protocols in different applications, even the same application by different groups lack of evaluation standard for the quality of EVs (such as integrity, concentration, stability, safety, regulatory responses)
Storage	Leakage of content with storage time and temperature possible damage of EVs by freezing and thawing
Drug delivery (pharmacokinetics and biodistribution)	Altered or contaminated exosomal cargos with culture proteins by passage, seeding densities, glucose conditions, and antibiotics in culture medium when cells used as a drug source lack of the feasibility road map to extrapolate the EVs dose for patients from preclinical models biodistribution patterns of EVs varied with injection route, and disease conditions possibility of thrombosis and hemostatic perturbations, and alloimmune responses and elimination of EVs by the reticuloendothelial system