TABLE 3.
Therapeutic potential of mitoEVs.
| Diseases | EV origins | Isolation methods | Characterization | Contents | Models | Effects | Refs |
|---|---|---|---|---|---|---|---|
| Severe emphysema | BMSCs | Differential ultracentrifugation | Marker: CD63, CD81(FC) Size: ∼150–250 nm (NTA) | Mitochondria | Elastase instilled mice | Reduced TGF‐β and IL‐1β levels, linear intercept between alveolar walls and the neutrophil cell count in lung tissue; Increased PAT/PET ratio and reduce the right ventricular area, which reduces cardiorespiratory dysfunction. | (Antunes et al., 2021) |
| Acute lung injury | BMSCs | Optical imaging | Size: 1–2 µm (IF) | Mitochondria | LPS‐induced ALI mice | Decreased leukocytosis, albumin leakage in the bronchoalveolar lavage; Induced lamellar body exocytosis and alveolar ATP production. | (Islam et al., 2012) |
| Adipose‐derived MSCs | Differential ultracentrifugation | Size: 50–150 nm (NTA, TEM) Marker: CD9, CD63, TSG101 (WB) | Mitochondria, mtDNA | LPS‐induced MH‐S macrophage; LPS‐induced ALI mice | Restored the macrophage mitochondrial function, inflammatory response (decreased IL‐6, TNF‐α, IL‐1β); Alleviated lung inflammation and lung damage. | (Xia et al., 2022) | |
| Acute respiratory distress syndrome | BMSCs | Differential ultracentrifugation | Size: 70–100 nm (NTA, EM) Marker: CD44, CD63 (FC) | Mitochondria | LPS‐induced HSAECs, HPMECs and PCLSs; LPS‐induced lung injury mice | Decreased IL‐8 level, alleviated mitochondrial function, barriers integrity and inflammatory response in vitro; Attenuated lung injury and lung mitochondrial function in vivo | (Su et al., 2021) |
| Anthracycline‐induced cardiomyopathy | BMSCs | Size‐based filtration | Size: 30–800 nm (NTA, TEM) Marker: CD9 (FC) | Mitochondria | DOX‐induced injury iCM; breast cancer survivors received DOX treated | Recovered cardiomyocyte viability, physiology and mitochondrial biogenesis and function in iCM; Improved myocardial function and remodelling in patients. | (O'Brien et al., 2021) |
| Myocardial infarction (MI) | Human iCM | Differential ultracentrifugation | Size: 100–600 nm (NTA, TEM) Marker: β1‐integrin, CD63 (FC) | Mitochondria; PGC‐1a and ERRγ mRNA | Hypoxia‐induced iCM; Artery ligated mice | Improved mitochondrial bioenergetics and biogenesis in iCM; Prevented cardiac remodelling of MI mice model | (Ikeda et al., 2021) |
| Sepsis | BMSCs | Differential centrifugation | Size: 100–1000 nm (TEM, NTA) Marker: Annexin V, CD29, CD73, CD90, CD105, CD45− (FC) | Mfn2, PGC‐1α and mitochondria | Cecal ligated and punctured rats; LPS‐induced IEC‐6 cells | Improved intestinal barrier dysfunction in sepsis rats; Restored mitochondrial dynamic balance in IEC‐6 cells | (Zheng et al., 2021) |
| Autoimmune encephalomyelitis | Neural stem cells | Differential ultracentrifugation, ultrafiltration, sucrose gradient ultracentrifugation and commercial kit | Size: 80–1000 nm (TEM, NTA)Marker: TSG101, PDC6IP, CD9, Golga2− (WB) | Mitochondrial proteins (ND2, ND5, etc.), mtDNA and mitochondria | MOG‐induced mice | Ameliorated neuroinflammation of autoimmune encephalomyelitis mice | (Peruzzotti‐Jametti et al., 2021) |
| Brain ischemic stroke | hCMEC/D3 cells | Differential ultracentrifugation | Size: 100–250 nm (DLS) | Mitochondria, ATP5A | OGD‐treated BECs | Increased ATP level and maximal OCR and ECAR of BECs | (D'Souza et al., 2021) |
| Acute kidney injury | BMSCs, hUC‐MSCs | Differential ultracentrifugation | Size: ∼50–500 nm (NTA, TEM) | TFAM mRNA, mtDNA, ATP5a1, COX IV, TOM20 | LPS‐induced HK‐2 cells; Bilateralrenal pedicle clamped and reperfusion mice | Attenuated mitochondrial dysfunction of HK‐2 cells; Attenuated renal dysfunction, inflammatory response and mitochondrial damage of AKI mice | (Zhao et al., 2021) |
| Marker: Alix, TSG101, HSP70 (WB) | |||||||
| Ischemic renal injury | STC‐like cells | Differential ultracentrifugation | Size: 100–300 nm (NTA) Marker: CD24, CD133, CD29, CD9, CD81 (WB) | Mitochondria | AMA‐induced injured TECs; Unilateral renal artery stenosis mice | Restored oxidative stress, and mtDNA level and DRP1 expression in injured TECs; Restored murine renal haemodynamics and function | (Zou et al., 2018) |
| Liver ischemia/reperfusion injury | hUC‐MSCs | Differential ultracentrifugation | Size: 100–700 nm (NTA, TEM) | Mitochondria | Liver IRI mice | Reduced ALT, AST and LDH level, attenuated liver injury and NETs formation | (Lu et al., 2022) |
| Marker: Alix, CD63, CD9, HSP70, GRP95− (WB) |
Abbreviations: ALI, acute lung injury; ALT, alanine transaminase; AMA, antimycin‐A; AST, aspartate transaminase; BECs, brain endothelial cells; BMSC, bone marrow‐derived stromal cells; DOX, doxorubicin; hCMEC/D3, human cerebral microvascular endothelial cell line; HSAECs, human small airway epithelial cells; HPMECs, human pulmonary microvascular endothelial cells; hUC‐MSCs, human umbilical cord mesenchymal stem cells; iCM, induced pluripotent stem cell‐derived cardiomyocytes; LDH, lactate dehydrogenase; LPS, lipopolysaccharide; MOG, myelin oligodendrocyte glycoprotein; MSCs, mesenchymal stem cells; OGD, oxygen‐glucose deprivation; PAT/PET ratio, pulmonary artery acceleration time/pulmonary artery ejection time ratio; PCLSs, precision cut lung slices; STC‐like cells, intrinsic renal scattered tubular cells; TECs, tubular epithelial cells.