Mesenchymal stem cell-derived extracellular vesicles as next generation drug delivery platforms

Figure 1 Biogenesis and composition of mesenchymal stem cell-derived extracellular vesicles. A: Extracellular vesicle biogenesis pathways showing the formation of exosomes via multivesicular bodies and microvesicles via plasma membrane budding; B: Major cargo components which together influence signaling and gene expression in recipient cells; C: Functional consequences relevant to therapeutic delivery. EV: Extracellular vesicle; MVBs: Multivesicular bodies; ILVs: Intraluminal vesicles; ESCRT: Endosomal sorting complex required for transport; miRNA: MicroRNA.

Figure 2 Engineering strategies for therapeutic cargo loading in mesenchymal stem cell-derived extracellular vesicles. A: Passive loading methods allow diffusion of small hydrophobic drugs into minimal structure disruption; B: Active loading techniques enhance cargo encapsulation through transient membrane permeabilization; C: Genetic and biogenic modification of parental mesenchymal stem cells allow selective incorporation of therapeutic molecules during extracellular vesicle formation; D: Surface engineering using targeting ligands, polyethylene glycol chains, or antibodies improve circulation duration, targeting precision, cellular uptake and tissue specific delivery. EV: Extracellular vesicle; siRNA: Small interfering RNA; MSC: Mesenchymal stem cell; PEG: Polyethylene glycol.

Figure 3 Translational flow and key challenges in clinical development of mesenchymal stem cell-derived extracellular vesicles therapeutics. Schematic representation of the essential phases in the clinical translation of mesenchymal stem cell-derived extracellular vesicles including mesenchymal stem cell expansion, scalable extracellular vesicle production, purification using techniques like tangential flow filtration and size-exclusion chromatography, and quality control assessment. Key translational challenges are also emphasized as essential factors affecting successful application in clinical setting. MSC: Mesenchymal stem cell; EV: Extracellular vesicle; TFF: Tangential flow filtration; SEC: Size-exclusion chromatography.