Table 1.

MSC-EVs in AKI.

In Vivo Model	EV-Source	EV Isolation Method	EV Route of Administration	EV Biological Effect/ Mechanism of Action	References
Glycerol mouse model Intra-muscular glycerol injection into inferior hind limbs (8 mL/kg)	BM-MSCs (15 µg/dose)	UC	Single intravenous injection 3 days after the damage	-Stimulation of renal cell proliferation	[19]
Cisplatin mouse model Subcutaneous cisplatin injection (12 mg/kg)	BM-MSCs (100 µg/dose)	UC	Single injection 8 h after the damage	-Reduction of apoptosis	[20]
IRI rat model Ligation of the left renal artery and vein for 45 min with contralateral nephrectomy	BM-MSCs (30 μg/dose)	UC	Single intravenous injection immediately after surgery	-Inhibition of renal cell apoptosis and stimulation of their proliferation -Amelioration of renal function	[21]
IRI mouse model Renal pedicle clamping for 30 min	h-UC-MSCs (100 µg/dose)	UC	Two intravenous injections after IRI	-miR-125b-5p/p53, promoted tubular repair targeting cell cycle and reduced apoptosis	[23]
IRI mouse model Renal pedicle clamping for 45 min	BM-MSCs (5 × 1010 EV/dose)	UC	Single tail intravenous injection 1 h before IRI	-miR-199a-3p protected the kidney by modulating Akt and Erk1/2 pathways	[24]
Cisplatin rat model Single intraperitoneal cisplatin injection (6 mg/kg)	UC-MSCs (200 µg/dose)	UC	Single injection in both the renal capsules 24 h damage	-Reduction of oxidative stress and apoptosis -Stimulation of cell proliferation	[25]
Sepsis mouse model Cecal ligation and puncture with CLP	UC-MSCs (120 μg/dose)	UC	Tail intravenous injection 3 h after CLP injury	-miR-140b up-regulation inhibited NF-kB pathway -Modulation of inflammation	[27]
IRI porcine model Unilateral ischemia for 120 min and contralateral nephrectomy	UC-MSCs (1 × 109 EV/dose)	UC and sequential 100 K Amicon centrifugal filter	Intravenous injection during the ischemia	-Reduction of STAT3 and NF-kB pathways -Expression of KLOTHO and BMP7	[28]
IRI rat model Left renal ischemia for 60 min	UC-MSCs (100 μg EV/dose)	UC	Caudal intravenous injection immediately after reperfusion	-CX3CL1 modulates macrophage accumulation	[29]
Sepsis mouse model Cecal ligation and puncture with CLP	A-MSCs (100 μg EV/dose)	UC	Tail intravenous injection	-Inhibition of inflammation and apoptosis -Modulation of the SIRT1 signaling pathway	[30]
LPS rat model Intraperitoneal injection of LPS (7.5 mg/kg)	BM-MSCs and A-MSCs (5 × 105 EV/dose)	UC	Single Injection 30 min before LPS injection	-Improved renal function and structure -Down-regulation of oxidative stress and inflammation	[31]
Unilateral IRI mouse model Renal artery clamping for 45 min	UC-MSCs (100 μg EV/dose)	UC	Caudal vein injection immediately after reperfusion	-Enhancement of pro-angiogenic activity in a HIF-1α-independent manner	[32]
IRI mouse model Bilateral renal pedicle clamping for 30 min	BM-MSCs and UC-MSCs (6.96 × 1010 EV/dose)	UC	Single-tail intravenous injection	-Reduction of mitochondrial damage -Down-regulation of inflammatory response	[33]
Glycerol mouse model Intramuscular glycerol injection into inferior hind limbs (8 mL/kg)	P-MSCs (80 µg EV/dose)	UC	Single tail intravenous injection 3 days after damage	-Modulation of mitochondrial damage	[34]
Rat kidney DCD ex vivo model	BM-MSCs	UC	Ex vivo EV perfusion	-Reduction of ischemic damage -Up-regulation of cell energy metabolism	[35]
IRI mouse model 35 min Left renal pedicle clamping for 35 min and contralateral nephrectomy	Gl-MSCs (400  ×  106 EV/dose)	UC	Single tail intravenous the administration immediately after surgery	-Recovery of renal function and structure	[36]

Abbreviations: Ultracentrifugation (UC), Ischemia and reperfusion injury (IRI), bone marrow mesenchymal stromal cells (BM-MSCs), human umbilical cord-MSCs (hUC-MSCs), adipose MSCs (A-MSCs), lipopolysaccharide (LPS), placental-MSCs (P-MSCs), glomerular MSCs (Gl-MSC), donor circulatory death (DCD).