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Review
. 2019 Dec 28;10(1):48.
doi: 10.3390/biom10010048.

Engineering Extracellular Vesicles as Nanotherapeutics for Regenerative Medicine

Lalithasri Ramasubramanian  1   2 , Priyadarsini Kumar  1   3 , Aijun Wang  1   2   3
Affiliations
Review

Engineering Extracellular Vesicles as Nanotherapeutics for Regenerative Medicine

Lalithasri Ramasubramanian et al. Biomolecules. .

Abstract

Long thought of to be vesicles that primarily recycled waste biomolecules from cells, extracellular vesicles (EVs) have now emerged as a new class of nanotherapeutics for regenerative medicine. Recent studies have proven their potential as mediators of cell proliferation, immunomodulation, extracellular matrix organization and angiogenesis, and are currently being used as treatments for a variety of diseases and injuries. They are now being used in combination with a variety of more traditional biomaterials and tissue engineering strategies to stimulate tissue repair and wound healing. However, the clinical translation of EVs has been greatly slowed due to difficulties in EV isolation and purification, as well as their limited yields and functional heterogeneity. Thus, a field of EV engineering has emerged in order to augment the natural properties of EVs and to recapitulate their function in semi-synthetic and synthetic EVs. Here, we have reviewed current technologies and techniques in this growing field of EV engineering while highlighting possible future applications for regenerative medicine.

Keywords: biomaterials; extracellular vesicles; regenerative medicine; stem cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Biogenesis of extracellular vesicles. Microvesicles and apoptotic bodies originate directly from the plasma membrane, while exosomes are derived from the endosomal compartments. intraluminal vesicles (ILVs) accumulate in the multivesicular bodies (MVBs) after early endosome maturation. Proteins, lipids, nucleic acids and other cargo are sequestered within the ILVs through an endosomal sorting complex required for transport (ESCRT)-dependent pathway. Eventually, MVBs fuse with the plasma membrane and release the ILVs into the extracellular space as exosomes.
Figure 2
Figure 2
Cell-derived nanovesicles. Whole cells are mechanically extruded to break the cell and create plasma membrane fragments. The fragments then self-assemble into nanovesicles that can retain intracellular molecules and surface makers.
Figure 3
Figure 3
Extracellular vesicle (EV)-mimicking liposomes can be engineered to mimic EV features by recreating the lipidomic profile (e.g., phospholipids, sphingolipids, cholesterol), and by conjugating proteins and receptors to recreate the targeting specificity. The liposomes can also be loaded with a variety of molecules, including proteins, siRNAs, miRNAs and small molecules, to recapitulate common EV cargo.
Figure 4
Figure 4
Biomimetic Polymer Nanoparticles. Cell plasma membrane that has been isolated and purified can be mixed with a polymer-based nanoparticle to create a cell-membrane-cloaked particle. Different types of cargo can be loaded within the polymer core.
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