Table 1.
Characteristics of included studies.
| Author (year); Country | Animal characteristics | PAIS model | Intervention characteristics | Control group | |||
|---|---|---|---|---|---|---|---|
| Species, Strain; Sex; Age | Age | MSCS source; Type | MSCS dose; Frequency | Day of administration; Mode | |||
| Cho et al. (2016);34 Korea | Mouse; CD-1 (ICR); 0 | 7 PND | Ligation rCCA; hypoxia (8% O2, 90 min) | NR | 1 × 105 cells; single | PND 42; intrastriatal | PBS; PBS-EE; MSC-EE |
| Ding et al. (2015);22 China | Rat; Wistar; NR | 7 PND | Double ligation + cut lCCA; 2 h recovery; hypoxia (8% O2, 2.5 h) | Placenta-derived MSCs | 5 × 105 cell/μL; single | PND 11; intracerebral | HIBD; HIBD + fibroblasts; Sham |
| Ding et al. (2017);23 China | Rat; Wistar; NR | 7 PND | Cut LCCA; hypoxia (8% O2, 2.5 h) | Placenta-derived MSCs | 5 × 104 cells/10 µL; single | PND 9; intracerebral | HIBD; HIBD + fibroblast group; Sham |
| Kim et al. (2012);35 Korea | Rat; Sprague–Dawley; 1 | 10 PND | Occlusion with silicone rubber; rMCA | MSCs from human umbilical cord | 1 × 105 cells; single | PND 10; intraventricular | PBS; Sham |
| Larpthaveesarp et al. (2021);37 USA | Rat; Sprague–Dawley; 0 | 10 PND | Dissection + 3 h occlusion with silicon-coated nylon filament; rMCA | Adipose-tissue-derived MSCs | 3 × 106 cells; single | PND 13; PND 17; intranasal | Sham; MCAO + media; MCCO + 3d MSC/EPO; MCAP + 3d EPO3; MCAO + 7d MSC/EPO; MCAP + 7d EPO3 |
| Lee et al. (2010);36 Korea | Rat; Sprague–Dawley; 1 | 7 PND | Double ligation + cut lCCA; 2 h recovery; hypoxia (8% O2, 3.5 h) | Human bone marrow mesenchymal stem cells | 1 × 106 cells; single | PND 10; intracardial | Sham + buffer; Sham-MSC; Hi-buffer |
| Li et al. (2014);24 China | Rat; Sprague–Dawley; 0 | 7 PND | 30 min ligation with reperfusion (4.0 suture); lCCA; NR; hypoxia (8% O2, 2.5 h) | Rats bone marrow mesenchymal stem cells | 1 × 106 cells; single | PND 8; intraperitoneal | Sham; PBS; Photon + MSC |
| Ohshima et al. (2015);40 Japan | Mouse; CB17; NR | 8 PND | Permanent occlusion; lCCA; 1 h recovery; hypoxia (8% O2, 30 min) | Rats bone marrow mesenchymal stem cells | 1 × 106 cells; single | PND 10; intravenous; intraperitoneal | MNC-intravenous; MNC-intraperitoneal |
| Sakai et al. (2018);41 Japan | Rat; Sprague–Dawley; 0 | 7 PND | double ligation (6.0 silk suture) and section lCCA; 1 h recovery; hypoxia (8% O2, 2 h) | Rats bone marrow mesenchymal stem cells | 1 × 106 cells; single | PND 10; intravenous | Sham; Vehicle |
| van Velthoven et al. (2017);38 USA | Rat; Sprague-Dawley; 0 | 10 PND | 1.5 h ligation (6.0 dermalon filament); ICA ; no hypoxia | Rat Sprague–Dawley bone marrow mesenchymal stem cells (GIBKO®) | 1 × 106 cells; single | PND 13; intranasal | Sham-Vehicle; Sham-MSC; Vehicle |
| van Velthoven et al. (2013);33 Netherlands | Rat; Sprague-Dawley; NR | 10 PND | 1.5 h double ligation (6–0 silk suture) and dissection of ICA | Rat Sprague–Dawley bone marrow mesenchymal stem cells (GIBKO®) | 1 × 106 cells; single | PND 13; intranasal | Sham-Vehicle; Sham-MSC; Vehicle; MSC-BDNF |
| van Velthoven et al. (2010);29 Netherlands | Mouse; C57Bl/6; NR | 9 PND | Occlusion; right carotid artery; hypoxia (10% O2, 45 min) | Bone marrow from femur and tibia of 6- to 8-week-old C57BL/6-Tg (UBC-GFP) 30 Sch/J mice | 1 × 105 in 2 µL PBS; single and repeated | PND 12; PND 17; intracerebral | Sham; Vehicle |
| van Velthoven et al. (2010);31 Netherlands | Mouse; C57Bl/6J; 0 | 9 PND | Permanent occlusion; right carotid artery; hypoxia (10% O2, 45 min) | Bone marrow from femur and tibia of 6- to 8-week-old C57BL/6-Tg (UBC-GFP) 30 Sch/J mice | 5 × 105 in 12 µL PBS | PND 17; intranasal | Vehicle |
| van Velthoven et al. (2010);32 Netherlands | Mouse; C57Bl/6; 0 | 9 PND | Occlusion; right carotid artery; hypoxia (10% O2, 45 min) | Bone marrow from femur and tibia of 6- to 8-week-old C57BL/6-Tg (UBC-GFP) 30 Sch/J mice | 1 × 105 in 2 µL PBS | PND 12; intracerebral | Sham; Vehicle |
| van Velthoven et al. (2012);30 Netherlands | Mouse; C57Bl/6J; NR | 9 PND | Occlusion; right carotid artery; hypoxia (10% O2, 45 min) | Bone marrow from femur and tibia of 6- to 8-week-old C57BL/6-Tg (UBC-GFP) 30 Sch/J mice | 1 × 105 in 2 µL PBS; repeated | PND 10; PND 17; intracerebral | Sham; Vehicle |
| Wei et al. (2015);39 USA | Rat; Wistar; 1 | 7 PND | Permanent ligation (10 silk sutures); distal branches MCA; cauterization rCCA | Bone marrow mesenchymal stem cells from Wistar rats – hypoxia preconditioned | 1 × 106 cells in 100 µL; repeated | PND 7; PND 10; intranasal | Shame; Saline |
| Xia et al. (2010);25 China | Rat; Sprague–Dawley; NR | 7 PND | Permanent ligation (6–0 surgical silk) lCCA; 3 h recovery; hypoxia (8% O2, 2.5 h) | Human umbilical cord blood mesenchymal stem cells | 5 × 104 µL; single | PND 10; intrecerebroparenchymal | Culture medium |
| Yang et al. (2020);28 China | Rat; Sprague-Dawley; NR | 7 PND | Permanent ligation (6–0 surgical silk) lCCA; 3 h recovery; hypoxia (8% O2, 2.5 h) | NR | 2 × 105 cells; single | PND 7; intracerebroventricular | Sham; PBS; siIL-6 MSCs; GFP MSCs |
| Zhang et al. (2014);26 China | Rat; Sprague-Dawley; NR | 7 PND | Ligation (6–0 surgical silk rCCA; 2–3 h recovery; hypoxia (8% O2, 2 h) | Human umbilical cord mesenchymal stem cells (Wharton’s jelly) | 5 × 105 cells; single; 5 × 106 cells; single | PND 8; PND 10; intravenous; intraperitoneal; different groups | Sham-Vehicle; HIE-vehicle 24 h; HIE-DFB |
| Zhou et al (2015);27 China | Rat; Sprague-Dawley; NR | 7 PND | According to Rice,21 no further description | Human umbilical cord mesenchymal stem cells | 2 × 105 cells; single | PND 12; intracerebroventricular | PBS; Sham |
0 = both sexes, 1 = male, 2 = female, NR not reported, PND postnatal day, rCCA right common carotid artery, lCCA left common carotid artery, MCA middle cerebral artery, MSC mesenchymal stem cell, MNC mononuclear cell, PBS phosphate-buffered saline, HIE hypoxic-ischemic encephalopathy, HIBD hypoxic-ischemic brain damage, EE enriched environment, EPO erythropoietin, DFB dermal fibroblasts, GFP green fluorescent protein, BDNF brain-derived neurotrophic factor.