TABLE 2.
The mechanisms and functions of ASC-exos in tissue regeneration.
| Disease | Source | Model | Function | Mechanism | References |
| Skin aging | Human ASC-CM | Photoaging-induced HDFs and HaCaTs | Photoaging prevention | Downregulate the activation and transcription of UVB-induced signaling pathways and upregulate the expression of antioxidant response elements | Li et al., 2019 |
| Human ASC-CM | Photoaging-induced HDFs | Photoaging prevention | PDGF-AA in ASC-CM promoted HDFs proliferation and activated PI3K/Akt signal pathway to facilitate ECM deposition and remodeling | Guo et al., 2020 | |
| Human BMSC-exos | Photoaging-induced HDFs and mice | Photoaging prevention | Produce ROS at a low level, downregulate TNF-α, upregulate TGF-β to increase MMP-1 and procollagen type I expression for collagen synthesis | Hu et al., 2019 | |
| Atopic dermatitis | Human ASC-exos | AD model of NC/NGA mice | Dermatitis improvement | Decrease the levels of inflammatory cytokines and reduce the number of eosinophils in the blood, and the infiltration of mast cells, dendritic epidermal cells | Cho et al., 2018 |
| Human ASC-exos | AD model of SKH-1 mice | Epidermal Barrier Repair | Reduce trans-epidermal water loss and enhance epidermal lamellar bodies and form lamellar layer at the interface of the SC and stratum granulosum. | Shin et al., 2020 | |
| Skin wound | Human ASC-exos | Skin lesion model of HaCaTs | HaCaTs viability enhancement | Foster HaCaTs proliferation, migration, and inhibit apoptosis through Wnt/β-catenin signaling pathway | Ma et al., 2019 |
| Human ASC-exos | Skin lesion model of HaCaTs and HDFs | HaCaTs and HDFs viability enhancement | ASC-exos containing MALAT1 could mediate H2O2-induced wound healing via targeting miR-124 through activating the Wnt/β-catenin pathway | He et al., 2020 | |
| Human ASC-exos | full-thickness skin wound of mice | Wound healing | Promote fibroblasts proliferation and migration and optimize collagen deposition via the PI3K/Akt signaling pathway to accelerate wound healing. | Zhang et al., 2018 | |
| Human ASC-exos | Diabetic foot ulcer of rat | Wound healing | ASC-exos overexpressing-Nrf2 promoted the proliferation and angiogenesis of endothelial cells, and increased the expression of wound growth factor, decreased the levels of inflammation and oxidative stress-related proteins. | Li X. et al., 2018 | |
| Human ASC-exos | Full layer skin wound of mice | Wound healing | ASC-exos overexpressing miRNA-21 enhanced the migration and proliferation of the HaCaTs by increasing the MMP-9 expression through the PI3K/AKT pathway | Yang et al., 2020 | |
| ASC-exos | Skin wound of diabetic mice | Wound healing | mmu_circ_0000250 enhanced the therapeutic effect of ASCs-exosomes to promote wound healing in diabetes by absorption of miR-128-3p and upregulation of SIRT1 | Shi et al., 2020 | |
| Scar formation | Human ASC-exos | Skin wound of mice | Scar removal | Inhibit collagen expression to reduce scar formation in the late stage of wound healing | Hu et al., 2016 |
| Human ASC-exos | Skin wound of mice | Scar removal | Regulate the ratios of type III collagen/type I collagen, TGF-β3/TGF-β1, and MMP-3/TIMP-1, as well as facilitating HDFs differentiation | Wang et al., 2017 | |
| Skin flap injury | Human ASC-exos | Artificial dermis prefabricated flap and leg wound of rat | Flap vascularization | Upregulation of miRNA-760 and downregulation of miRNA-423-3p in ASC-exos could regulate the expression of ITGA5 and HDAC5 genes, respectively, to promote the vascularization of the skin flap | Xiong et al., 2020 |
| Skin flap I/R injury | Human ASC-exos | Skin flap I/R injury of mice | Flap repair | IL-6 highly contained in ASC-exos could enhance skin flap recovery and angiogenesis after I/R injury | Pu et al., 2017 |
| Human ASC-exos | Skin flap I/R injury of mice | Flap repair | H2O2-treated ASC-exos increased the neovascularization and relieve the inflammation and apoptosis of the flap after I/R injury | Bai et al., 2018 | |
| Bone defect | Human ASC-exos | Hypoxic-ischemic osteocyte | Osteogenesis | Ameliorate osteocyte apoptosis and osteocyte-mediated osteoclastogenesis by lowering the expression of RANKL | Ren et al., 2019 |
| Human ASC-exos | Calvarial defects of rats | Bone formation | ASC-exos overexpressing miRNA-375 were absorbed by hBMSCs, and inhibit the expression of IGFBP3 to exert osteogenic effects | Chen S. et al., 2019 | |
| Human ASC-exos | Human primary osteoblastic cells | Bone formation | TNF-α-preconditioned ASC-exos promoted the proliferation and differentiation of human osteoblasts through the Wnt signaling pathway | Lu et al., 2017 | |
| Osteoarthritis | Human ASC-exos | OA model of osteoblasts | Inflammation improvement | Downregulate SA-β-gal activity and the accumulation of γH2AX | Tofiño-Vian et al., 2017 |
| Human ASC-exos | Chondrocytes stimulated with H2O2 | Chondrogenesis | Downregulated the pro-inflammatory markers IL-6, NF-κB and TNF-α, while they upregulated the anti-inflammatory cytokine IL-10 when co-cultured with activated synovial fibroblasts, promoted chondrogenesis in periosteal cells and increased collagen type II and β-catenin | Zhao et al., 2020 | |
| Obesity | Mouse ASC-exos | Obese mice | Obesity prevention | Activate M2-type macrophage polarization, improve inflammation, and promote the browning of white adipose tissue | Zhao et al., 2018 |
| Fat grafting | Human ASC-exos | Mice | Fat grafts survival promotion | Hypoxia-treated ASC-exos enhanced the angiogenesis by regulating the VEGF/VEGF-R signaling pathway | Han et al., 2019 |
| Mouse ASC-exos | Mice | Fat grafts survival promotion | Promote angiogenesis and up-regulate early inflammation, exert proadipogenic effect and increase collagen synthesis during the mid to late stages | Chen S. et al., 2019 | |
| Breast cancer | Human ASC-exos | Breast cancer MCF-7 cells | Tumor progression | Activate the Wnt and Hh signaling pathways to strengthen the growth of MCF-7 cells | Lin et al., 2013 |
ASCs, Adipose-derived stem cells; ASC-exos, ASC-derived exosomes; HDFs, Human Dermal Fibroblasts; HaCaTs, Human Keratinocytes; UVB, Ultraviolet B; ASC-CM, ASC-Conditioned Medium; ECM, Extracellular Matrix; H2O2, Hydrogen Peroxide; PDGF-AA, Platelet-Derived Growth Factor-AA; ROS, Reactive Oxygen Species; MMP-1/9, Matrix Metalloproteinase 1/9; TNF-α, Tumor Necrosis Factor Alpha; TGF-β, Transforming Growth Factor Beta; IL-4/5/6/13, Interleukin 4/5/6/13; VEGF, Vascular Endothelial Growth Factor; Nrf2, NF-E2-related factor 2; TIMP-1, Tissue Inhibitor of Metalloproteinases-1; I/R, Ischemia-Reperfusion; RANKL, Receptor Activator of Nuclear Factor Kappa B Ligand; SA-β-gal, Senescence-Associated β-galactosidase; γH2AX, Phosphorylated Histone H2AX; Bcl-2, B-cell lymphoma/leukemia 2; Bax, Bcl-2-associated X protein.