Table 3.
Comparison of different upstream modifications for increased exosome production and their reported fold increase and effects.
| Upstream Modifications | Fold Increase | Alterations and Effects | References |
|---|---|---|---|
| Soluble Factors | |||
| Lipopolysaccharide (LPS) | 1.37 | Upregulation of let-7b increased immunotherapeutic effect | [62] |
| N-methyldopamine and norepinephrine | 3 | No significant change | [63] |
| Serotonin and calcium | 2–2.5 | - | [64] |
| Adiponectin | 3 | Present in exosomes | [65] |
| ATP | 4 | No significant change | [66] |
| Wnt3a | - | Present in exosomes; increased neuroprotective abilities |
[67] |
| Plant ceramide | 2.5 | - | [68] |
| Chemical/physical stimulation | |||
| Hypoxia | 1.5 | Dependent on cell type; increased expression of nucleic acids and proteins | [71,72,74,75] |
| Serum deprivation | Varies | Decreased exosome protein content | [52,76] |
| Flow/stretch | 37 | Over 200 proteins expressed differently from typical exosomes | [77,78] |
| High-frequency ultrasound | 8–10 | Increased exosome protein content | [79] |
| 3D cultivation | |||
| 3D spheroid culture | 2–3 | - | [80] |
| Microcarrier-based suspension | 20; 140 with tangential flow system | No significant change | [52,81,82,83] |
| 3D print fibrillar scaffold with perfusion system | 100 | Decreased exosome protein content | [84] |
| Low-shear unsubmerged 3D-printed polylactic acid lattice matrix | 2 | Maintained protein expression | [85] |
| Biomaterials | |||
| Nitric oxide-releasing polymer | Not significant |
Enhanced pro-angiogenic activity | [86] |
| Lithium-incorporated bioactive glass ceramic | Not significant |
Enhanced pro-angiogenic activity | [87] |
| Iron-oxide coated poly-lactic-co-glycosidic acid (PLGA) nanoparticle | 2 | Increased antioxidant or tissue regeneration factors | [88] |
| Bioglass | 2 | Modulation of cargo through altered expression of microRNA; enhanced ability to promote vascularization | [89] |
| EXOtic | ~6.8 | - | [69] |