Table 1.

Application of engineered extracellular vesicles in injury

Cell source	Tissue	Specific components	Modification methods	Biological effects	publication date	Reference
USCs	cartilage	miR-140–5p	gene engineering	Overexpression of miR-140-5p and alleviation of OA progression by down-regulating VEGFA.	2022	Liu et al.51
ADSCs	cartilage	curcumin	incubation	Reduce oxidative stress and protect chondrocytes.	2022	Xu et al.142
BMSCs	cartilage	miR-216a-5p	hypoxia	Cartilage repair in osteoarthritis via delivery of miR-216a-5p.	2021	143
BMSCs	cartilage	circRNA_0001236	gene engineering	Up-regulate circRNA _0001236 and inhibit cartilage degradation through miR-3677-3p/Sox9	2021	Mao et al.144
M1 macrophage	bone	miR-21a-5p	gene engineering	The osteogenic differentiation of MC3T3-E1 was accelerated by directly targeting GATA2 with miR-21a-5p.	2023	Luo et al.145
M2 macrophages	bone	H2S	incubation	H2S induced the polarization of M2 macrophages and modified the protein profile of exosomes, with a significant enrichment of the moesin protein.	2023	Zhou et al.146
BMSCs	bone	miR-26a	gene engineering	Promoting bone regeneration by suppressing genes associated with osteoclast differentiation instead of causing harm to osteoclasts.	2023	Kuang et al.147
U937	bone	Cathelicidin/LL-37	gene engineering	Engineered exosomes possess enhanced antimicrobial and angiogenic activities, and more effectively promote proliferation and migration of skin cells.	2022	Su et al.148
BMSCs	bone	RGD	incubation	Synergistic effects of EVs and RGD enhance osteogenic differentiation and mineralization of BMSCs in vitro.	2022	Ma et al.108
BMSCs	bone	miR-935	gene engineering	Targeting STAT1 by delivery of miR-935 promotes osteoblast proliferation and differentiation.	2021	Zhang et al.109
BMSCs	muscle	IL6ST	incubation	Selective inhibition of IL6 signaling pathway, thereby inhibiting STAT3 phosphorylation.	2021	Conceição et al.149
PMSCs	muscle	collagen-binding peptide SILY	click chemistry	Enhanced adhesion of EVs to collagen surface.	2022	Hao et al.150
C2C12	muscle	miR-29b	gene engineering	Prevent muscle atrophy induced by dexamethasone, angiotensin II and tumor necrosis factor alpha.	2022	Chen et al.151
BMSCs	muscle	TGF-β1	incubation	Targeting FABP3 by delivery of miR-29a.	2022	Xu et al.152
Fibroblasts	nerve	TFAP2C	COS Incubation	COS induce fibroblasts to produce TFAP2C-enriched exosomes, which are then transferred into axons to promote axon regeneration via miR-132-5p/CAMKK1.	2023	Zhao et al.153
BMSCs	nerve	SIRPα	gene engineering	Accelerating hematoma clearance and improving secondary white matter injury following intracerebral hemorrhage.	2023	Gao et al.154
UCMSCs	nerve	miR-146a-5p	gene engineering	Promoting neurological recovery in rats with acute spinal cord injury by targeting neurotoxic astrocytes.	2022	Lai et al.155
HEK293	nerve	Tom40	gene engineering	Protect cells reduce oxidative stress.	2022	Sayeed et al.52
ADSCs	nerve	miR-25	Oxygen-glucose deprivation	Promoting differentiation, maturation and migration of oligodendrocyte precursor cells.	2021	Zhai et al.53
VSC4.1	nerve	miR-126-3p	Oxygen-glucose deprivation	The up-regulated miR-126-3p may have a protective effect by regulating PI3K/Akt and NF-κB signaling pathways mediated by PIK3R2.	2021	Wang et al.156
ADSCs	vascular	circ-Snhg11	hypoxia	Circ-Snhg11 regulates the migration, proliferation, and vascular regeneration potential of vascular endothelial cells through the miR-144-3p/NFE2L2/HIF1α pathway.	2023	Hu et al.157
ADSCs	vascular	FPG3	electrostatic and hydrophobic interaction	Enhancing the biological function of extracellular vesicles in cell migration and angiogenesis	2023	Ma et al.158
BMSCs	vascular	islet-1	gene engineering	Increased retention of extracellular vesicles in endothelial cells and enhanced resistance to apoptosis, proliferation and angiogenesis.	2022	Hu et al.54
DPSCs	vascular	LOXL2	hypoxia	Up - regulated LOXL2 may be involved in angiogenesis mediated by engineered extracellular vesicles.	2022	Li et al.17
UCMSCs	liver	HSTP1	gene engineering	Precise treatment of hepatic stellate cells in complex liver tissues.	2022	Lin et al.159
A549	lung	ACE2	gene engineering	Surface protein receptors mediate host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens.	2022	Ching et al.160
PSCs	lung	siRNA	electroporation	Specific targeting of lung tissue and inhibition of SARS-CoV-2 pseudovirus infection in vivo.	2022	Fu et al.161
plasma	colon	siRNA	gene engineering	Rapidly alleviates intestinal inflammation by inhibiting pro-inflammatory responses in colon macrophages and T cells.	2022	Zhou e al.162
ADSCs	corneal	miRNA 24-3p	gene engineering	Accelerate corneal epithelial defect healing and epithelial maturation	2023	Sun et al.163

ACE2, angiotensin-converting enzyme 2; ADSCs, adipose-derived mesenchymal stem cells; Akt, protein kinase B; A549, adenocarcinomic human alveolar basal epithelial cells; BMSCs, bone marrow mesenchymal stem cells; C2C12, mouse myoblast cell line; COS, chitosan oligosaccharides; FPG3, fluorinated peptide dendrimers; HIF1α, hypoxia inducible factor-1α; HSTP1, HSTP1 peptide; IL6ST, interleukin 6 cytokine family signal transducer; LOXL2, lysyl oxidase homolog 2; NFE2L2: nuclear factor, erythroid 2 like 2; NF-κB, nuclear Factor kappa B; OA, osteoarthritis; PI3K, phosphatidylinositol 3-kinase; PIK3R2, phosphoinositide-3-kinase regulatory subunit 2; PSCs, pluripotent stem cells; RGD, Arg-Gly-Asp; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SIRPα, signal regulatory protein α; STAT1, signal transducer and activator of transcription 1; TFAP2C, transcription factor AP-2 gamma; Tom40, mitochondrial membrane protein; UCMSCs, umbilical cord mesenchymal stem; USCs, urine-derived stem cells; U937, human macrophage cell line; VSC4.1, spinal cord anterior horn motor neuron tumor cells.