|
| Pretreatment | Source | Potency | Molecular mechanism | Ref. |
|
| EP4-antagonist | hBMSC | Promoting neurogenesis and neuritogenesis in damaged hippocampi. | Increasing conversion of 2,3-cAMP to adenosine and promoting β3-tubulin polymerization in vitro. | [96] |
| Metformin | hBMSC | Ameliorating disc cell senescence in vitro and optimizing the potential for the treatment of IDD. | Metformin-induced AMPK activation induces the phosphorylation of SNAP29, which in turn mediates the transfer of ITIHT4 to MVBs, leading to the accumulation of ITIH4 in the released exosomes. | [97] |
| Glycyrrhetinic acid (GA) | AD-MSC | Promoting therapeutic effect against acute liver ischemia-reperfusion injury. | / | [98] |
| Kartogenin | BMSCs | Promoting the effect on cartilage regeneration in a rat OA model. | Reduction of the expression of COLI in chondrocytes. | [99] |
| Thrombin | HUCB-MSC | Boosting the biogenesis of MSC-derived EVs and enriching their cargo contents. | These effects are achieved via PAR-1-mediated pathways and partly via the PAR-1-independent, PAR-3-mediated activation of Rab5, EEA-1, and the ERK1/2 and AKT signaling pathways. | [100] |
| Oridonin | BMSC | Improving the therapeutic potential against ischemia-reperfusion injury in rats. | These effects are achieved through participating in the autophagic process of cardiomyocytes | [101] |
| Heme oxygenase-1 (HO-1) | hBMSC | Improving the efficacy of exosomes to alleviate myocardial infarction (MI) | Expression of miR-183-5p in exosomes is elevated and then inhibiting cardiomyocyte senescence through regulation of HMGB1/ERK pathway | [102] |
| Atorvastatin (ATV) | BMSC | Enhancing biological functions of endothelial cells in the treatment of diabetic skin defects. | These effects are achieved via the AKT/eNOS pathway by upregulating miR-221-3p. | [103] |
| Atorvastatin (ATV) | BMSC | Exhibiting more potent cardioprotective function in a rat model of AMI. | These effects are achieved through the upregulation of long noncoding RNA H19. | [104] |
| Melatonin | BMSC | Promoting microglia to M2-like polarization and alleviating spinal cord injury. | Ubiquitin-specific protease 29 (USP29) increases markedly in exosomes and stabilizes nuclear factor-like 2 (NRF2). | [105] |
| Melatonin | BMSC | Improving functional recovery and vessel repair in a murine hindlimb ischemia model with CKD. | Increasing the expression of cellular prion protein [PrP (c)] in exosomes. | [106] |
| Melatonin | hBMSC | Promoting diabetic wound healing. | Activating the PTEN/AKT signaling pathway. | [107] |
| Melatonin | BMSC | Improving the therapeutic potential against renal ischemia-reperfusion injury in rats. | / | [108] |
| Blue light | HUC-MSC | Promoting proangiogenic ability in murine matrigel plug and skin wound models. | Upregulation of miR-135b-5p and miR-499a-3p in MSC-exosomes. | [112] |
| Extrusion | AD-MSC | Improving robust bone regeneration effects in mouse nonhealing calvarial defects. | Inhibition of miR-29a in MSC-exosomes. | [113] |
| Bioglass | hBMSC | Promoting vascularization of endothelial cells and facilitating intradermal angiogenesis. | Decreasing microRNA-342-5p, while increasing microRNA-1290 in MSC-exosomes. | [114] |
| Titanium surfaces | hBMSC | Inducing elevated secretion of exosomes and enhancing angiogenesis in vitro | Increasing the expression of angiogenesis-related factors in exosomes | [109] |
| Low-intensity pulsed ultrasound (LIPUS) | BMSC | Enhancing the effect of exosomes on cartilage regeneration in osteoarthritis | These benefits are achieved by inhibiting the activation of the nuclear factor-κB (NF-κB) pathway | [110] |
| PG/TCP (PEGMC with β-TCP) | BMSC | Promoting osteogenesis and spinal fusion | / | [111] |
|
