Table 2.

Characteristics of included preclinical studies for meta-analysis.

Author's name	Country	Year	Animal Model	Sex	Human/Animal	Exosome source	Passage number	Characterization	Isolation method	Exosome size	Exosome marker	Endosomal origin markers	Induced method	Concentration	Exosome admin.	End point	Outcome	Ref.
Wang H et al.	USA	2019	C57BL/6 mice	N/A	Animal	Primary mouse satellite cells	P2	NTA	Centrifugation + Filtration	91 ± 1.9 nm		Tsg101	I.M.	N/A	3rd day	14 days after injection	Exo/miR29 improves skeletal muscle atrophy and reduces kidney fibrosis by suppressing YY1 and TGF-b pathway proteins.	[49]
Liu X et al.	USA	2019	C57BL/6 mice	Male	Human	HKC-8	N/A	TEM	Ultracentrifugation	30–100 nm	CD63	TSG101	I.V.	20 mg/kg	1st day	11th day after injection	Tubule-derived exosomes contribute to renal fibrogenesis by transporting Sonic Hedgehog (Shh) ligand.	[45]
Liu B et al.	China	2020	SD rats	Male	Human	hUCMSCs	P3	TEM	Centrifugation + Filtration	50–100 nm	CD9, CD63 & CD81	NA	I.C.	200 μg	N.A.	14th day after injection.	HucMSC-Ex attenuated UUO-induced renal fibrosis and tubular cell apoptosis by inhibiting the ROS-mediated p38MAPK/ERK signaling pathway.	[44]
Wang Y et al.	China	2020	Bred Fisher rats	N/A	Animal	BM-MSCs	P2	N/A	Centrifugation + Filtration	N/A	CD44, CD29	Alpha 4-integrin	I.V.	N/A	0 day	14th day after injection.	MiR-294/miR-133 overexpression prevented TGF-β1-induced epithelial-mesenchymal transition in HK2 cells by inhibiting SMAD2/3 and ERK1/2 phosphorylation.	[24]
Zhao M et al.	China	2021	SD Rats	N/A	Animal	Rat urine sample	N/A	TEM, NTA	Ultracentrifugation	30–150 nm	CD63, CD81	NA	I.V.	12.50 g/kg	N.A.	18weeks after injection	MHCD mitigated renal fibrosis in IgA nephropathy rats by suppressing the TGF-β1/Smad3 pathway through exosomal downregulation of TGF-β1 expression.	[39]
Jin J et al.	China	2021	C57BL/6 mice	Female	Human	BM-MSCs	N/A	TEM, NTA	Exosome Isolation Kit	50–150 nm	CD 9, CD 81	NA	I.V.	50 μg	Twice a week	28th day	MSC exosomal anti-let-7i-5p combats TGF-β1-induced fibrosis in NRK52E cells and UUO-induced renal fibrosis in vivo.	[47]
Liu L et al.	China	2021	C57BL/6 mice	Male	Human	PSC-MSCs	P3∼8	NTA	Centrifugation + Filtration	10∼150 nm	CD90, CD45, CD105 & CD19	NA	I.V.	1 × 1011 (Particle amount)	N.A.	14th day after injection.	Upregulating SIRT6 expression while downregulating β-catenin and its downstream products.	[48]
Liu L et al.	S. Korea	2021	BALB/c mice	Male	Human	AD-MSC	P2	TEM, NTA	Exosome isolation kit	173.02 ± 2.34 nm	CD81 & CD9	NA	I.V.	100 μg	twice a week for 2 weeks	3rd week after administration	Exocue treatment downregulated CKD-related miRNAs, improving kidney function via aquaporin upregulation and reduced urea and creatinine levels.	[41]
Liu Y et al.	China	2022	SD rats	Male	Human	BM-MSCs	P4∼6	TEM, NTA	Centrifugation + Filtration	30–150 nm	CD9, CD63, & CD81	NA	I.V.	150 μg/week	Once a week	16th week	BMSC-Exo strengthened si-Smurf2's protective effect against TGF-β1-induced fibrosis.	[36]
Zheng H et al.	China	2022	C57BL/6 mice	Male	Human	293 cell line human embryonic kidney cells	N/A	TEM	Ultracentrifugation	100 nm	CD63, CD81	NA	I.V.	100 μg	Once a week	28th day	Exo-miR-26a relieved kidney-downregulated miR-26a expression, tubular injury, and aldosterone (ALD)-induced TIF.	[40]
Alasmari W et al.	Saudi Arabia	2022	Albino rats	Female	Animal	BM-MSCs	P3	TEM	Centrifugation + Filtration	70 nm	CD63, CD81	NA	I.V.	100 μg	24 h after ovariectomy	8th week	Exosomes hinder CKD progression by lowering gene expression of NGAL, TGF-β1, and α-SMA.	[37]
Liang M et al.	China	2022	C57BL/6 mice	N/A	Human	HK-2 cells proximal tubular cell line	N/A	TEM, NTA	Centrifugation + Filtration	100–150 nm	CD63	TSG101	I.V.	N/A	twice weekly for 4 weeks	28th day	MiR-374a-5p hinders renal fibrosis progression by modulating the MAPK6/MK5/YAP axis.	[38]
Lu Y et al.	China	2023	BALB/c mice	Male	Animal	Mouse renal tubular cell line TCMK-1	N/A	TEM	Ultracentrifugation	145.8 nm	HSP70, CD63	TSG101	I.V.	100 μg	Per day for 5 days	7th day	TGF-β-induced TECs co-cultured with macrophages led to M1 polarization. Exosomes from TECs without TGF-β or with TGF-β alone did not induce M1 macrophage markers.	[34]
Wang Z et al.	China	2023	C57BL/6 mice	Male	Human	hucMSCs	N/A	TEM, NTA	Ultracentrifugation	30–150 nm	CD63,	Tsg101, & Alix	I.V.	100 μg	Once 7 days after surgery	14th day	Inhibited expression of proteins related to the Wnt/β-catenin signaling pathway.	[35]
Y. Wan et al.	China	2023	SD Rats	Male	Human	hucMSCs	P5	TEM, NTA	Ultracentrifugation	30–150 nm	CD63	Tsg101, & Alix	I.V.	250 μg	Immediately after reperfusion	24 h after injection	HucMSC-Ex reduced pyroptosis-related proteins (NLRP3, GSDMD, caspase-1, and IL-1β) in renal tissue of IRI rats.	[46]
Xi Liu et al.	China	2023	C57BL/6 mice	Male	Human	HKC-8	N/A	TEM, NTA	Ultracentrifugation	30–150 nm	CD63	Tsg101	I.V.	200 μg	Once in 2 days	14th day	Exo-TNFAIP8 promotes fibroblast survival by inducing p53 degradation and stimulating proliferation.	[43]
Di Yin et al.	China	2023	C57BL/6 mice	Male	Animal	Tubular epithelial cells of mouse	N/A	TEM, NTA	Ultracentrifugation	129.5 ± 8.2 nm	CD63, CD9	Tsg101, & Alix	I.P.	200 μg	Once on day 1	3rd day	Quercetin inhibits exosome release, exerting renoprotective effects by suppressing Hsp70 or Hsp90.	[42]

Abbreviations: N/A: not applicable; I.V.: intravenous; IM: Intramuscular; I.C: Intracellular; IP: Intraparietal; HKC-8:Human proximal tubular epithelial cells; HbMSCs: Human bone marrow derived; hucMSCs: Human umbilical cord mesenchymal stem cells; AD: Human adipose; PSC-MSCs: pluripotent stem cell-derived mesenchymal stem cells.