Table 2.
Pre-intervention to improve the function of exosomes in the treatment of diabetes.
| Disease and animal | Cell type releasing Exo | Intervention | Pathways | Effect: in virto | Effect: in vivo | Effect on inflammation /immune system | ref |
|---|---|---|---|---|---|---|---|
| Diabetic cutaneous wound, Rat | hAMSCs | miR-21-5p overexpressing | Wnt/β-catenin pathways ↑ | proliferation and migration of keratinocyte cells ↑ | vessel growth and maturing ↑, wound healing process ↑ | inflammatory cell infiltration↓ | (121) |
| Diabetic wound, Mice | hAMSCs | hypoxia | PI3K/Akt pathways ↑ | fibroblast proliferation and migration ↑ | re-epithelialization ↑ | CD31↑, TGF-β ↑, COLI ↑ and COLIII ↑, IL-6 ↓ | (27) |
| Diabetic full-thickness excisional wound, Mice | ADSCs | mmu_circ_0000250-overexpressing | miR-128-3p/SIRT1 pathway↑ | HG-induced EPC apoptosis ↓, autophagy of EPC ↑ | wound closure ↑ | SIRT1-mediated anti-inflammatory ↑ | (24) |
| Diabetic foot ulcer, Mice | ADSCs | mmu_circ_0001052 overexpressing | miR-106a-5p ↓, FGF4/p38MAPK pathway ↑ | proliferation ↑, migration and angiogenesis of high glucose-induced HUVEC ↑ | speed of healing ↑ | NA | (122) |
| Diabetic foot ulcer, Rat | ADSC | Nrf2 overexpression | SMP30 ↑, VEGF ↑, p-VEGFR2 ↑, ROS ↓ | increased cell viability ↑, tube formation of EPCs ↑ | Ulcerated area ↓, angiogenesis ↑, inflammation ↓, oxidative stress ↓ | IL-1β ↓, IL-6 ↓, TNF-α ↓ | (123) |
| Diabetic full-thickness wounds, Rat | BMSC | atorvastatin pretreated | AKT/eNOS pathway ↑ | endothelial cell angiogenesis↑ | Ascularization ↑ , the wound healing ↑ | NA | (124) |
| Diabetic full thickness dermal dorsal defect, Rat | BMSC | pioglitazone-pretreated | PI3K/AKT/eNOS pathway ↑ | migration and tube formation ↑, wound repair ↑, VEGF expression of HUVEC ↑ | diabetic wound healing ↑, angiogenesis ↑ | NA | (125) |
| Diabetic full-thickness dermal defect, Rat | BMSC | melatonin-pretreated | PTEN/AKT pathway ↑ | ratio of M2 polarization to M1 polarization in RAW264.7 cells ↑ | angiogenesis and collagen synthesis ↑ | ratio of M2 / M1 polarization ↑,IL-1β ↓, TNF-α ↓, IL-10 ↑, Arg-1 ↑ | (106) |
| Diabetic punch biopsy excisional wound, Mice | BMSC | HOTAIR overexpressing | NA | HOTAIR ↑,VEGF ↑ in endothelial cells | angiogenesis ↑ and wound healin ↑ | NA | (125) |
| Diabetic foot ulcer, mice | BMSC | lncRNA H19 overexpression | miR-152-3p-mediated PTEN inhibition ↓ | apoptosis and inflammation of fibroblasts ↓ | flammatory cells ↓, granulation tissues thicker around the wound | IL-10 ↑, IL-1b ↓, TNF-a ↓ | (33) |
| diabetic wounds rat | HEK293 | miR-31-5p overexpression | HIF1AN ↓, EMP-1↓ | cell proliferation ↑ and migration ↑ in ECs, HFF-1 cells and HaCaT cells; capillary-like construction activity ↑ in ECs | proangiogenesis ↑, profi ↑, brogenesis ↑, reepithelization↑ | NA | (126) |
| Diabetic cutaneous wound, Rat | UC-MSC | Lipopolysaccharide-pretreated | M2 macrophage polarization ↑ through let-7b via TLR4/NF-κB/STAT3/AKT pathway | converted inflammatory THP-1 cells to M2 polarization | inflammatory cell infiltration ↓, new small capillaries and woundhealing ↑ | anti-inflammatory cytokines ↑, M2 macrophage activation ↑ | (127) |
hAMSCs, human adipose-derived mesenchymal stem cells; ADSCs, adipocyte-derived stem cells; ADSC, adipocyte-derived stem cell; BMSC, bone mesenchymal stem cells; HEK293, human embryonic kidney 293T cells; UC-MSC, Umbilical cord-derived mesenchymal stem cells; PI3K, phosphatidyl-inositol 3-kinase; AKT, protein kinase b; SIRT1, silent information regulator 1; FGF4, fibroblast growth factor 4; p38MAPK, P38 mitogen-activated protein kinase; SMP30, senescence marker protein 30; VEGF, vascular endothelial growth factor; VEGFR2 , vascular endothelial growth factor receptor 2; ROS, reactive oxygen species; eNOS, endothelial nitric oxide synthase; NA, ot applicabl; HIF1AN, hypoxia inducible factor 1 subunit alpha inhibitor; EMP-1, EPO mimetic peptide-1; TLR4, toll-like receptor 4; NF-κB,nuclear factor kappa-B; STAT3, Signal transducer and activator of transcription 3; EPC, endothelial progenitor cells; HUVEC, human umbilical vein endothelial cells; VEGF, vascular endothelial growth factor; HOTAIR, HOX transcript antisense RNA; ECs, early career specialists; THP, human monocytic-leukemia cells; CD31, platelet endothelial cell adhesion molecule-1; TGF-β, transforming growth factor β; COLI, Collagen I; IL-6, Interleukin 6; IL-1β, Interleukin-1β; TNF-α,Tumor Necrosis Factor-α; IL-10, Interleukin-10; Arg-1, Arginase 1; IL-1b, Interleukin-1β.