Table 2.
Preclinical in vivo studies on the immune modulatory and regenerative effects of MSC-extracellular vesicles (EVs).
| Source of EVs | Methodology | Results | Reference |
|---|---|---|---|
| Rat BM-derived MSCs | Rat Acute Kidney Injury (AKI) induced by gentamicin (G). | Improved renal histology and function. | [ 60] |
| Human embryonic stem cell-derived MSCs | Myocardial infarction in mice. | Reduced infarct area. | [ 61] |
| Human BM-derived MSCs | AKI induced by ischemia-reperfusion injury in rats. | Improved renal histology and function. | [ 62] |
| Human BM-derived MSCs | In vitro: EVs on cisplatin-induced apoptosis of human renal tubular epithelial cells. | In vitro: EVs up-regulated in cisplatin-treated human tubular epithelial cells anti-apoptotic genes, and down-regulated genes leading to cell apoptosis. | [63] |
| In vivo: Cisplatin-induced AKI. | In vivo: Improved renal function and histology, improved survival. | ||
| Human UC-derived MSCs cultured under hypoxia | Rat hindlimb ischemia model. | Improved blood flow recovery. | [ 64] |
| Murine BM-derived MSCs | Hypoxia-induced pulmonary hypertension in rats. | Inhibition of vascular remodeling and of hypoxic pulmonary hypertension. | [ 65] |
| Human umbilical cord mesenchymal stem cells | In vitro: treatment with cisplatin alone in NRK-52E cells. | In vitro: Reversal of cisplatin induced apoptosis and oxidative. | [66] |
| In vivo: cisplatin-induced Acute Kidnay Injury (AKI) rat models. At 24 h after treatment with cisplatin, EVs injected into the kidneys. | In vivo: Improved kidney histology and biochemical parameters of kidney function. | ||
| Human BM-derived MSCs cultured under hypoxia | Acute myocardial infarction rat model. | Improved blood flow recovery, reduced infarct size and preserved cardiac systolic and diastolic performance. | [ 67] |
| Human UC-derived MSCs | Rat model of skin deep second-degree burn wound. | EV-treated wounds exhibited accelerated re-epithelialization, with increased expression of CK19, PCNA, collagen I (compared to collagen III). Activation of Wnt/β-catenin by hucMSC-; Wnt4 was found in MSC-EVs, and promoted β-catenin nuclear translocation and activity to enhance proliferation and migration of skin cells. | [ 68] |
| Human BM-derived MSCs | DSS-induced colitis in mice. | Improved body weight and clinical score, reduced colon shortening, reduced TNFα, IL-1β and COX-2 expression in colon mucosa. | [ 69] |
| Rat BM-derived MSCs | TNBS-induced colitis in rats. | Improved body weight and clinical score, reduced colon shortening, improved histology, reduced TNFα, IL-1β, COX-2 and increased IL-10 in colon mucosa. | [ 70] |
| Human BM-derived MSCs | Hypoxic-ischemic injury of the preterm brain in lamb fetuses. | Improved brain function by reducing the total number and duration of seizures, and by preserving baroreceptor reflex sensitivity, tendency to prevent hypomyelination. | [ 71] |
BM = Bone Marrow; UC = Umbilical Cord; DSS = Dextran sulfate sodium; TNBS = 2,4,6-trinitrobenzenesulfonic acid.