Table 1.

Clinical applications of exosomes in drug delivery and regenerative medicine.

	Drug delivery	Regenerative medicine
Definitions	In which exosomal cargo is modified to contain a specific compound, including but not limited to a particular protein, miRNA, or pharmaceutical drug, for treatment	In which exosomes are used as naturally produced for treatment
Number of Papers	360	338
Number of Clinical Trials	2	13
Pros	Highly specific organotropic behaviour [6,15] Biocompatible [6] Can be engineered to increase drug load or improve stability and targeting ability [6,12,15] Stable during cryopreservation [16] Naturally crosses cell membranes and the BBB [30,54] Avoid macrophage uptake, resulting in long blood circulation [54] Large surface area to volume ratio allows exosomes to carry a significant amount of surface cargo [4] Can carry hydrophobic and hydrophilic drugs [15]	Highly specific organotrophic behaviour [40,48,54, B. 18,26] Nonimmunogenic [54] Can be selected to carry specific proteins, receptors, or nucleic acids for gene therapy via cell culture microenvironment [9,16,35,64, B. 26] Stable during cryopreservation [16] Naturally crosses cell membranes and the BBB [63] Regulate tissue homoeostasis [36,54] Initiates tissue repair and regeneration [2,17,34,36,40,48] Released by most cell types, enabling tissue-specific signalling [48,54] Long-lasting paracrine effects [39,40]
Cons	Difficult to produce enough yield to be effective in humans [6] All isolation techniques have cons, including time, monetary cost, forming aggregates, introducing contaminants [6,54] Systemic administration has not reflected targeting potential [6]	Difficult to produce enough yield to be effective in humans [10,64] All isolation techniques have cons, including time, monetary cost, forming aggregates, introducing contaminants [16,63,66] No single way to manufacture exosomes of a specific potency [10,16]
Representative Companies	Anjarium Biosciences ArunA Biomedical Codiak Biosciences Evox Therapeutics Exogenus Therapeutics	Aegle Therapeutics BreStem Therapeutics Capricor Therapeutics Kimera Exosomes ReNeuron Tavec Pharma Xollent Biotech