Engineered extracellular vesicles for ischemic stroke: a systematic review and meta-analysis of preclinical studies

Li, Pengtao; Yin, Rui; Chen, Yihao; Chang, Jianbo; Yang, Lang; Liu, Xiaoyu; Xu, Houshi; Zhang, Xiao; Wang, Shihua; Han, Qin; Wei, Junji

doi:10.1186/s12951-023-02114-8

Table 1 Summary of studies included in the systematic review

From: Engineered extracellular vesicles for ischemic stroke: a systematic review and meta-analysis of preclinical studies

Study	Specie/gender/age/weight	Number	Stroke model	Characteristics of EVs				Therapeutic method			Duration
Study	Specie/gender/age/weight	Number	Stroke model	Source	Diameter(nm)	Methods of engineered	Engineering targets	Route	Dose	Time	Duration
Deng et al., 2019 [21]	C57BL/6J mice, 8-10w, M	40	Suture	MSC	NA	Transfection	Cell	IV	NA	24 h-14d	14d
Guo_1 et al., 2020 [22]	SD rat, M, 250-300 g	39	Suture	Blood	150–165	Ultrasonic	EV	IV	10 mg/kg	24 h-7d	28d
Guo_2 et al., 2021 [23]	SD rat, M, 250-300 g	36	Suture	Blood	NA	Surface modification	EV	IV	NA	Immediately	24 h
Huang et al., 2020 [24]	SD rat, M	84	Suture	Blood	81.8-133.9	Ultrasonic	EV	IV	1.6 mg	48 h	1d
Jiang et al., 2022 [25]	T2DM	28	Electrocoagulation	NSC	146 ± 17	Coculture	EV	Transcranial	10μL	2 h	21d
Kim_1 et al., 2019 [26]	SD rat, 10w, M, 280-320 g	30	Suture	Soma	143.5 ± 5.7	Electroporation	EV	IV	30 μg	Before 18 h	24 h
Kim_2 et al., 2020 [27]	SD rat, 9w, M, 250-300 g	34	Suture	MSC	194.2 ± 44.5	Coculture	Cell	IV	200 μg	Immediately	28d
Kim_3 et al., 2021 [28]	SD rat, 10w, M, 280-320 g	56	Suture	Soma	39.1 ± 5.1	Transfection	Cell	Nasal	75 μg	2 h	3d
Lee et al., 2016 [29]	SD rat, M, 200-250 g	42	Suture	MSC	NA	Coculture	Cell	IV	0.2 mg/kg	48 h	7d
Li et al., 2020 [30]	SD rat, M, 250-300 g	135	Suture	Blood	68.06 ± 1.94	Coculture	EV	IV	3 mg/kg	24 h-7d	7d
Liu et al., 2022 [31]	SD rat, M, 250-280 g	45	Suture	Blood	NA	Ultrasonic	EV	IV	0.75 mg	Immediately	24 h
Pan et al., 2020 [32]	C57BL/6J mice, 6-8w, M	40	Suture	MSC	24.8-169.3	Transfection	Cell	IV	1 × 10¹⁰	1.5 h	4d
Shi et al., 2022 [33]	SD rat, 8-12w, M, 250-300 g	84	Suture	MSC	99.2–388.0	Coculture	EV	Transcranial	100 lg/kg	24 h-3d	28d
Wang et al., 2020 [34]	T2DM, 8-10w, M, 42-48 g	143	Suture	MSC	129.4 ± 19.9	Transfection	Cell	IV	50 μg	2 h	14d
Wei et al., 2022 [35]	SD rat, M, 280-320 g	24	Suture	MSC	30–100	Transfection	Cell	Transcranial	5μL	Immediately	21d
Xin_1 et al., 2017 [36]	Wistar rat, 2-3 m, M, 270-300 g	24	Suture	MSC	NA	Transfection	Cell	IV	100 μg	24 h	28d
Xin_2 et al., 2021 [37]	Wistar rat, 2-3 m, M, 250-300 g	30	Suture	MSC	NA	Transfection	Cell	IV	100 μg	24 h	28d
Xu_1 et al., 2020 [38]	C57BL/6J mice, M, 25 ± 2 g	32	Suture	MSC	30–100	Transfection	Cell	IV	400 μg	Immediately	7d
Xu_2 et al., 2022 [17]	C57BL/6J mice, 9.2 ± 0.4w, M, 23 ± 1.2 g	24	Suture	NSC	100–150	Transfection	Cell	IV	100uL	2 h	24 h
Yang_1 et al., 2020 [39]	C57BL/6J mice, 8-10w, M, 24-26 g	430	photochemistry	Soma	117.3 ± 4.8	Transfection	Cell	IV	12 mg/kg	24 h	28d
Yang_2 et al., 2020 [40]	SD rat, M, 280-350 g	118	Suture	MSC	30–210	Transfection	Cell	IV	100 μg	24 h	14d
Yang_3 et al., 2022 [41]	C57BL/6J mice, M, 20-25 g	24	Suture	MSC	28–211	Transfection	Cell	IV	10 μg	Before 24 h	2 h
Yoon et al., 2022 [42]	SD rat, 8w, M, 300-330 g	60	Suture	NSC	39.9-339.8	Transfection	Cell	IV	300 μg/ kg	2 h	24 h
Zhang et al., 2020 [43]	SD rat, 8w, M, 240-280 g	38	Suture	NSC	126.1 ± 7.2	Coculture	Cell	Transcranial	4 × 10⁹	24 h	14d
Zhao et al., 2020 [44]	SD rat, M, 260-280 g	24	Suture	MSC	30–150	Transfection	Cell	IV	200μL	24 h and 14d	28d
Zhou_1 et al., 2022 [45]	SD rat, 6-8w, M, 200-240 g	NA	Suture	MSC	30–200	Transfection	Cell	IV	NA	2 h	28d
Zhou_2 et al., 2023 [46]	C57BL/6J qmice, 9-10w, M, 23-27 g	36	Suture	MSC	100	Transfection	Cell	Nasal	10uL	2 h	28d
Zhu et al., 2022 [47]	SD rat, 8w, M, 250-280 g	60	Suture	NSC	30–200	Coculture	EV	Transcranial	10μL	72 h	28d

SD rat: Sprague-Dawley rat; T2DM: type 2 diabetes mellitus mice; M: Male; BMSC: Bone marrow mesenchymal stem cell; NSC: Neural stem cell; IV:Intravenous injection; NA: Not Applicable

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