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

Table 2 Mesenchymal stem cell-derived extracellular vesicles as platforms for drug delivery

Engineering/delivery strategy	Therapeutic cargo	Target disease/application	Delivery route	Major advantages over synthetic nanoparticles	Challenges	Ref.
Native MSC-EV therapy	Endogenous miRNAs, proteins	Cardiovascular, renal, liver injury	Intravenous	Natural biocompatibility. Low immunogenicity	Biodistribution to liver and spleen	[9,105]
Surface engineered exosomes	Targeting ligands	Tissue-specific targeting	Systemic	Enhanced homing and target specificity	Manufacturing scalability	[106,107]
CRISPR/Cas9 delivery via MSC-EVs	CRISPR/Cas9 gene-editing components	Gene editing applications	Experimental systemic delivery	Ability to cross biological barriers	Cargo loading efficiency	[108,109]
KRAS G12D siRNA-loaded exosomes (iExosomes)	siRNA	Metastatic pancreatic cancer	Intravenous (clinical trial)	Tumor-specific gene silencing	Standardization and dose control	NCT03608631[110]
MSC-exosomes loaded hydrogel	Exosomes-containing growth factors	Full thickness cutaneous wound healing and skin regeneration	Local/topical application	Sustained release, improved stability and retention enhanced wound closure, angiogenesis	Direct injection of exosomes, need for suitable carrier system, limited prior studies on hydrogel encapsulated exosomes	[97]
Bioreactor-based MSC culture	Bulk EV production	Clinical translation	GMP-scale	Increased yield	Phenotypic variability	[111,112]
MSC-EV spray formulation	Regenerative factors	Myocardial infarction (large animals)	Topical/local cardiac	Minimally invasive administration	Stability and storage validation	[113-117]
MSC-EVs vs synthetic nanoparticles comparison	Endogenous therapeutic cargo	Broad therapeutic use	Multiple routes	Reduced toxicity, better barrier penetration	Heterogeneity and pharmacokinetics	[108]

MSC-EV: Mesenchymal stem cell-derived extracellular vesicle; miRNA: MicroRNA; siRNA: Small interfering RNA; GMP: Good manufacturing practice.