Table 3.
Effects of Engineered Exosomes in Kidney Disease Models
| Source | Disease | Model | Approach | Identification | Effects | Reference |
|---|---|---|---|---|---|---|
| AMSCs (Human) | AKI | Vivo: BALB/c, cisplatin | Metabolic glycoengineering-mediated click chemistry | NMR spectroscopy | Specifically bind to the overexpressed CD44 in AKI and target the damaged kidneys | [126] |
| Vitro: HK-2, cisplatin | ||||||
| PMSCs (Human) | AKI | Vivo: C57BL/6, IRI | Hydrogels | Rheology tests | RGD peptides enhanced exosome stability and target cell uptake efficiency, and alleviated kidney injury by inhibiting CASP3 | [127] |
| Vitro: HK-2, H/R, RAW263.7, LPS+IFN-γ | ||||||
| RBCs (C57BL/6J) | AKI, CKD | Vivo: C57BL/6J, IRI, UUO | Phage | Western blot | Engineered exosomes can reduce inflammation and fibrosis by targeting Kim-1 to accumulate in damaged renal tubules and deliver siRNAs of transcription factors P65 and Snai1 | [128] |
| Vitro: HEK293, TECs, n/s | ||||||
| Satellite cells (C57BL/6J) | CKD | Vivo: C57BL/6J, UUO | Adenovirus | n/s | miR-29 restored the decrease in the mass of the soleus, tibialis anterior, and EDL muscles induced by UUO and alleviated kidney fibrosis by targeting TGF-β3 | [129] |
| BMSCs (Human) | n/s | Vitro: HEK293, normal | Freeze-thaw and direct mixing | Fluorescence microscopy | Hybrid exosomes have higher transfection efficiency | [130] |
| UCMSCs (Human) | AKI | Vivo: ICR, cisplatin | Sonication | Fluorescence resonance energy transfer | Enhanced the uptake rate and targeting of exosomes, promoted the proliferative activity of NRK52E cells, and alleviated renal oxidation and inflammation | [131] |
| Vitro: NRK52E, cisplatin | ||||||
| AMSCs (Human) | CKD | Vivo: Nu/nu, UUO | Lentivirus vector | Fluorescence microscopy | Activated the PI3K/Akt/eNOS signaling pathway, relieved renal hypoxia and oxidative stress, inhibited EndoMT, and reduced renal fibrosis | [132] |
| Vitro: HUVECs, hypoxia condition | ||||||
| KMSCs (FVB/N) | CKD | Vivo: FVB/N, renal anaemia | Lentiviral vector | Fluorescence microscopy and qRT-PCR | Increased hemoglobin levels in CKD mice and downregulated the infiltration of F4/80-positive macrophages | [133] |
| Vitro: MDCK, PMC, HK-2, normal | ||||||
| BMSCs (Human) | AKI | Vivo: SCID, glycerol | Electroporation | QRT-PCR | Reduced the amount of exosomes required for treatment, alleviated tubular necrosis and hyaline tubular formation | [134] |
| Vitro: TECs, H/R | ||||||
| UCMSCs (Human) | DN, CKD | Vivo: C57BL/6, STZ | Electroporation | UV–spectrophotometry | Induced CD4+Treg cells to regulate intestinal microbiota metabolism to reduce kidney injury | [135] |
| Orange | IgAN | Vivo: BALB/c, SEB, BSA | Electroporation | UV-spectrophotometry | Reduced proteinuria, alleviated mesangial hyperplasia and IgA deposition, and decreased the percentage of LIGHT+CD4+ cells | [136] |
| Vitro: PPs, ConA, IL-2 | ||||||
| ToMCSs (Human) | CKD | Vivo: ICR, 5/6 nephrectomy | CRISPR-Cas9 system | Thermogravimetric analysis | Engineered exosomes promote stem cell migration and tubule and blood vessel generation by targeting CXCR4 | [137] |
Abbreviations: ConA, concanavalin A; EDL, extensor digitorum longus; EndoMT, endothelial-to-mesenchymal transition; eNOS, endothelial nitric oxide synthase; ERCs, endometrial regenerative cells; IgAN, immunoglobulin A nephropathy; KMSCs, kidney mesenchymal stem cells; LTH, linear tubular homing peptide; NMR, nuclear magnetic resonance; PMC, peritoneal mesothelial cells; PPs, peyer’s patches; qRT-PCR, quantitative real-time polymerase chain reaction; RBCs, red blood cells; R-Exos, RBCs-exosomes; RGD, arginine-glycine-aspartic acid peptide; SEB, staphylococcal enterotoxin B; ToMCSs, tonsil mesenchymal stem cells; UV-Vis, ultraviolet-visible spectrophotometry.