Table 1.
Characteristics of included studies.
| Study | Strain and Species | Brain Injury Model | Term vs Pre-term Model | Age Injury Induced | UCB Cell Source & Type | Route of Administration | Total Cells per Dose | Cell Administration Time Post-injury | Comparator |
|---|---|---|---|---|---|---|---|---|---|
| Ahn 2013 [24] | Sprague-Dawley rats | IVH | Pre-term | PND4 | Human MSCs | Intraventricular | 1 × 105 | 2 days | Injury + PBS |
| Ahn 2015 [25] | Sprague-Dawley rats | IVH | Pre-term | PND4 | Human MSCs | IC or IV | 1 × 105 (IC) or 5 × 105 (IV) | 2 days | Injury + NS |
| Ahn 2018 [26] | Sprague-Dawley rats | Meningitis | Term | PND11 | Human MSCs | Intraventricular | 1 × 105 | 6 h | Injury + NS |
| Ahn 2021 [27] | Sprague-Dawley rats | IVH | Pre-term | PND4 | Human MSCs | Intraventricular | 1 × 105 | 2 days | Injury + PBS |
| Aridas 2016 [28] | Merino Border Leicester cross sheep | HI | Term | 139-141 days of gestation | Sheep MNCs | Arterial | 1 × 108 | 12 h after birth | Injury + no vehicle |
| Baba 2019 [29] | NOD/SCID mice | HI | Term | PND9 | Human MNCs | IV | 5 × 106 | 21 days | Injury + PBS |
| Bae 2012 [30] | Sprague-Dawley rats | HI | Term | PND7 | Human MNCs | IV | 1 × 107 | 1 day | Injury + PBS |
| Chang 2021 [31] | NOD/SCID mice | HI | Term | PND9 | Human CD34+ or CD34- HSCs | IC | 1 × 105 | 12 h | Injury + no vehicle |
| Cho 2020 [32] | ICR mice | HI | Pre-term | PND7 | Human MNCs | IP | 3 × 107 | 7 days | Injury + no vehicle |
| Choi 2021 [33] | ICR mice | HI | Pre-term | PND7 | Human MNCs | IP | 3 × 107 | 7 days | Injury + PBS |
| Dalous 2013 [34] | Sprague-Dawley rats | Excitotoxic brain injury | Pre-term | PND5 | Human MNCs | IP or IV | 106, 3 × 106 or 107 (IP) 106 or 107 (IV) | 1 or 24 h (IP), 6 or 24 h (IV) | Injury + saline |
| De Paula 2009 | Wistar rats | HI | Term | PND7 | Human MNCs | IV | 1 × 107 | 1 day | Injury + saline soln |
| De Paula 2012 [36] | Wistar rats | HI | Term | PND7 | Human MNCs | IV | 1 × 106, 1 × 107 or 1 × 108 | 1 day | Injury + vehicle |
| Drobyshevsky 2015 [37] | New Zealand white rabbits | HI | Pre-term | 22 days of gestation | Human MNCs | IV | 2.5 × 106 or 5 × 106 | 4 h after birth | Injury + saline |
| Geissler 2011 [38] | Wistar rats | HI | Term | PND7 | Human MNCs | IP | 1 × 107 | 1 day | Injury + NS |
| Ghaffaripour 2015 [39] | Wistar rats | HI | Term | PND14 | Human MNCs | IV | 2 × 105 | 7 days | Injury + saline soln |
| Grandvuillemin 2017 [40] | Sprague-Dawley rats | HI | Term | PND7 | Human MNCs or ECFCs | IP | 1 × 107 (MNC) or 5 × 105 (ECFC) | 2 days | Injury + saline soln |
| Greggio 2014 [41] | Wistar rats | HI | Term | PND7 | Human MNCs | Arterial | 1 × 106 or 1 × 107 | 1 day | Injury + vehicle |
| Hattori 2015 [42] | Wistar rats | HI | Term | PND7 | Human MNCs | IP | 1 × 107 | 6 h | Injury + vehicle |
| Kadam 2015 [43] | CD1 mice | HI | Term | PND12 | Human CD34+ enriched MNCs | IP | 1 × 105 | 2 days | Injury + vehicle |
| Kidani 2016 [44] | SCID mice | HI | Pre-term | PND7 | Human CD133+ cells | IP | 1 × 105 | 1 day | Injury + NS |
| Kim 2012 [45] | Sprague-Dawley rats | HI | Term | PND10 | Human MSCs | Intraventricular | 1 × 105 | 6 h | Injury + PBS |
| Kim 2016 [46] | Sprague-Dawley rats | Hyperoxia | Pre-term | PND0-14 | Human MSCs | Intratracheal | 1 × 105 | PND5 | Injury + NS |
| Ko 2018 [47] | Sprague-Dawley rats | IVH | Pre-term | PND4 | Human MSCs | Intracerebroventricular | 1 × 105 | 2 days | Injury + NS |
| Li 2014 [48] | Sprague-Dawley rats | HI | Pre-term | PND7 | Human MNCs or CD34+ cells | IV | 1.5 × 106 | 7 days | Injury + saline |
| Li 2016 [49] | Merino-Border Leicester cross sheep | HI | Pre-term | 102.2 ± 0.3 days of gestation | Sheep MNCs | IV | 5 × 107 | 12 h or 5 days | Injury + saline |
| Li 2017 [50] | Merino-Border Leicester cross sheep | HI | Pre-term | 102.2 ± 0.3 days of gestation | Sheep MNCs | IV | 5 × 107 | 12 h | Injury + saline |
| Li 2018 [51] | Merino-Border Leicester cross sheep | HI | Pre-term | 102.2 ± 0.2 days of gestation | Sheep MNCs | IV | 5 × 107 | 12 h | Injury + saline |
| Lyu 2022 [52] | Unspecified rats | HI | Term | PND7 | Human MNCs | IV | 1 × 107 | 1 day | Injury + NS |
| Malhotra 2020 [15] | Border Leicester- Merino cross sheep | FGR | Pre-term | 88 days of gestation | Sheep MNCs | IV | 2.5 × 107 | 1 h after birth | Injury + saline |
| McDonald 2018 [14] | Sprague-Dawley rats | HI | Term | PND7 | Human MNCs, Tregs, monocytes, EPCs | IP | 1 × 106 (MNCs) or 2 × 105 (other) | 1 day | Injury + PBS |
| Meier 2006 [53] | Wistar rats | HI | Term | PND7 | Human MNCs | IP | 1 × 107 | 1 day | Injury + NS |
| Nakanishi 2017 [54] | Sprague-Dawley rats | HI | Term | PND7 | Rat MNCs | IP | 2 × 106 | 3 days | Injury + PBS |
| Ohshima 2016 [55] | CB-17 SCID mice | HI | Pre-term | PND8 | Human CD34+ cells | IV | 1 × 105 | 2 days | Injury + PBS |
| Park 2015 [56] | Sprague-Dawley rats | HI | Pre-term | PND7 | Human MSCs | Intraventricular | 1 × 105 | 6 h | Injury + no vehicle |
| Park 2016 [57] | Sprague-Dawley rats | IVH | Term | PND4 | Human MSCs | Intraventricular | 1 × 105 | 2 or 7 days | Injury + PBS |
| Paton 2018 [58] | Border Leicester-Merino cross sheep | Chorioamnionitis | Pre-term | 95 days of gestation | Human MNCs | IV | 1 × 108 | 6 h | Injury + saline |
| Paton 2019 [59] | Border Leicester-Merino cross sheep | Chorioamnionitis | Pre-term | 95 days of gestation | Human MNCs | IV | 1 × 108 | 6 h | Injury + saline |
| Penny 2019 [60] | Sprague-Dawley rats | HI | Term | PND7 | Human MNCs | IP | 1 × 106 | 1 day | Injury + PBS |
| Penny 2020 [61] | Sprague-Dawley rats | HI | Term | PND10 | Human MNCs | Intranasal or IP | 1 × 106 | 1 day (1 dose group) or 1, 3 and 10 days (3 dose group) | Injury + saline |
| Penny 2021 [62] | Sprague-Dawley rats | HI | Term | PND10 | Human MNCs | Intranasal or IP | 1 × 106 | 1, 3 and 10 days | Injury + saline |
| Pimentel-Coelho 2010 [63] | Lister-Hooded rats | HI | Term | PND7 | Human MNCs | IP | 2 × 106 | 3 h | Injury + vehicle |
| Purohit 2021 [64] | New Zealand white rabbits | IVH | Pre-term | 3–4 h after birth | Human unrestricted somatic stem cells | Intraventricular | 2 × 106 | 18 h | Injury + saline |
| Rosenkranz 2012 [65] | Wistar rats | HI | Term | PND7 | Human MNCs | IP | 1 × 107 | 1 day | Injury + vehicle |
| Rosenkranz 2013 [66] | Wistar rats | HI | Term | PND7 | Human MNCs | IP | 1 × 107 | 1 day | Injury + vehicle |
| Tsuji 2014 [67] | CB-17 SCID mice | Ischaemic stroke | Term | PND12 | Human CD34+ cells | IV | 1 × 105 | 2 days | Injury + PBS |
| Vinukonda 2019 [68] | New Zealand white rabbits | IVH | Pre-term | 3-4 h after birth | Human unrestricted somatic stem cells | Intraventricular or IV | 2 × 106 (intraventricular) or 1 × 106 (IV) | 18 h | Injury + saline |
| Wang 2013 [69] | Sprague-Dawley rats | HI | Term | PND7 | Human MNCs | Intraventricular | 3 × 106 | 1 day | Injury + PBS |
| Wang 2014 [70] | Sprague-Dawley rats | HI | Term | PND7 | Human MNCs | Intraventricular | 3 × 106 | 1 day | Injury + PBS |
| Wasielewski 2012 [71] | Wistar rats | HI | Term | PND7 | Human MNCs | IP or intrathecal | 1 × 107 | 1 day | Injury + saline |
| Xia 2010 [72] | Sprague-Dawley rats | HI | Term | PND7 | Human MSCs | IC | 1 × 105 | 3 days | Injury + vehicle |
| Yasuhara 2010 [73] | Sprague-Dawley rats | HI | Term | PND7 | Human MNCs | IV | 1.5 × 106 | 7 days | Injury + PBS |
| Yu 2019 [74] | Sprague-Dawley rats | HI | Term | PND7 | Human MNCS or CD34+ cells | IV | 1 × 106 (MNCs) or 1.5 × 104 (CD34+) | 7 days | Injury + PBS |
| Zhang 2019 [75] | Sprague-Dawley rats | HI | Term | PND7 | Human MNCs | Intraventricular | 1 × 107 | 1 day | Injury + PBS |
| Zhang 2020 [76] | Sprague-Dawley rats | HI | Term | PND7 | Human MNCs | Intraventricular | 3 × 106 | 1 day | Injury + NS |
Abbreviations: ECFC, endothelial colony forming cells; EPCs, endothelial progenitor cells; FGR, foetal growth restricted; HI, Hypoxia Ischaemia; HSCs, haemopoietic stem cells; IC, intracerebral; ICR, institute for cancer research; IP, intraperitoneal; IV, intravenous; IVH, intraventricular haemorrhage; MNCs, mononuclear cells; MSCs, mesenchymal stem cells; NS, normal saline; NOD, nonobese diabetic; PBS, phosphate buffered saline; PND, post-natal day; SCID, severe combined immunodeficient; soln, solution; Tregs, T regulatory cells.; UCB, umbilical cord blood.