**1. Introduction**

Extracellular vesicles (EVs) represent a heterogenous population of vesicles that include exosomes and the plasma membrane shedding microvesicles (MVs) (also known as microparticles) and apoptotic bodies. Exosomes represent the smallest subtype of EVs and have spherical bodies with a lipid bilayer membrane. Exosome formation begins in endosomes as the budding of the endosomal membrane results in the formation of multivesicular bodies (MVBs) [1]. The fusion of MVBs with the inner leaflet of the plasma membrane results in the release of intraluminal vesicles (ILVs) as exosomes (**Figure 1**) [1]. The ILVs within the lumen of the endosomes have three fates [2]. First, the contents can be used for the biogenesis of specialized lysosome-related organelles such as melanosomes. Second, the ILVs may fuse with lysosomes. Third, the ILVs may fuse with the plasma membrane to release the content

#### **Figure 1.**

*Biogenesis of EV's. Microvesicles and apoptotic bodies are generated by outward budding of the cell's plasma membrane. Exosomes are formed from the endocytic pathway of the cell. In this process early endosomes undergo inward budding to form intraluminal vesicles (ILVs) inside the late endosomal vesicles (LEVs) or multivesicular bodies (MVBs). The fate of the MVBs include degradation by lysosomes, fusion with autophagosomes, or fusion with the plasma membrane of the cell resulting in the release of the ILVs to the extracellular space in the form of exosomes. As shown, MVBs and autophagosomes can be degraded by lysosomes.*

into the extracellular space in which the vesicles will then be termed exosomes. There are a number of signaling and specialized proteins that contribute to the biogenesis of exosomes. The biogenesis of microvesicles and apoptotic bodies is different from that of exosomes as these vesicles are produced from the shedding or budding of the plasma membrane from the parent cell (**Figure 1**). The release of EVs from a cell can be triggered by a myriad of stimuli. Importantly, not all EVs are created equally and EVs found in biological fluids including plasma and urine represent a heterogenous mixture of subpopulations of EVs. The fate of EVs after they are released from their parent cell is to either be taken up by a neighboring or distant cell or to be excreted from the body.
