RNAi Therapeutic Delivery by Exosomes - RNA Interference from Biology to Therapeutics - page 187

Fig. 9.1 Cellular origins of membrane vesicles. Diagram summarizing the cellular origin of mem-
brane vesicles. Microvesicles arise from budding of the cell membrane. Exosomes are released from
MVBs, while apoptotic blebs are released from the disintegrating membranes of apoptotic cells

to detach from cellular actin ending with fission of the stalk [ 33 ] . This shedding is
not passive and requires energy input, RNA synthesis, and protein translation [ 37 ] .
The resultant microvesicles contain cytosol and an extracellular membrane surface
in the same orientation and topology as that of their donor cells so that their signal-
ing properties reflect those of their cell of origin [ 38 ] . The membrane composition
undergoes remodeling during the formation of these vesicles.

9.3.2 Apoptotic Blebs

Apoptotic blebs/bodies are released directly from the plasma membrane when it
buds from disintegrating apoptotic cells. During the process of programmed cell
death, there is an alteration in cell morphology, shrinkage of the cytoplasm, and
nuclear condensation, and the final stage is cell fragmentation into apoptotic blebs,
which enclose remnants of the shrinking cell. The number of apoptotic blebs cor-
relates with the degree of apoptosis in cultured cells [ 39 ] . These are irregular in
shape, and their size can vary between as low as 50 nm to a controversial maximum
size of 500 nm [ 40 ] to 5 m m [ 41 ]. Phosphatidylserine is externalized as in MVs
which encourages phagocytic recognition by other cells [ 42 ] . Although sharing
some features with MVs, apoptotic blebs, in contrast to MVs, can contain cytosolic
organelles and possible nuclear fragments [ 43 ] .