Table 1.
Summary of therapeutic effects of combining cell therapy and rehabilitation (excluding brain stimulation) on motor function in animal models of stroke.
| Reference | Model | Cell Therapy | Rehabilitation | Outcome | |||||
|---|---|---|---|---|---|---|---|---|---|
| Transplanted Cell | Cell Mass and Location | Timing of Transplantation | Category | Onset | Duration | Interactive Effect on Motor Function | Mechanism | ||
|
Hicks et al. [35] (2007) |
MCAO in rats | Stem cells from mSVZ | 8 × 105 cells, ipsilateral sensorimotor cortex and striatum | 7 days after MCAO | Enriched environment | 8 days after MCAO | 30 days | n.a. | ↑Migration of transplanted cells |
| Hicks et al. [36] (2008) |
Endothelin-1 induced MCAO in rats | Stem cells from mSVZ | 8 × 105 cells, ipsilateral sensorimotor cortex and striatum | 7 days after MCAO | Enriched environment | 8 days after MCAO | 3 months | n.a. | Majority (~99%) of cells died within 2 months of transplantation |
| Hicks et al. [37] (2009) |
dMCAO in rats | hESC-derived NPCs | 8 × 105 cells, ipsilateral sensorimotor cortex | 7 days after dMCAO | Enriched environment | 8 days after MCAO | 66 days | No effect | Poor survival of transplanted cells |
| Seo et al. [38] (2013) |
Hypoxic-ischemic brain injury in mice | hASCs | 1 × 105 cells, ipsilateral striatum | 5 weeks after injury | Enriched environment | 5 weeks after injury | 8 weeks | Synergistic | ↑Neurogenesis in striatum ↑Astrocytic activation |
| Zhang et al. [39] (2015) |
MCAO in rats | rMSCs | 3 × 106 cells, intravenously | 1 day after MCAO | Treadmill exercise (4 m/min for the 1st day, 8 m/min for the 2nd day, 12 m/min for the remaining days for 20 min, every day) |
2 days after MCAO | 12 days | Synergistic | ↓Apoptosis |
| Cho et al. [40] (2016) |
Hypoxic-ischemic brain injury in mice | hASCs | 1 × 105 cells, ipsilateral striatum | 5 weeks after injury | Enriched environment | 5 weeks after injury | 8 weeks | Synergistic | ↑Angiogenesis ↑Astrocytic activation |
| Sasaki et al. [41] (2016) |
MCAO in rats | rMSCs | 1 × 106 cells, intravenously | 6 hours after MCAO | Treadmill exercise (3 m/min for 20 min, every day for 1 week. Speed was increased by 3 m/min every week) |
1 day after MCAO | 34 days | Synergistic | ↓Infarction volume ↑Corpus callosum thickness ↑Synaptogenesis |
| Zhao et al. [42] (2018) |
MCAO in rats | rADSCs | 2 × 106 cells, intravenously | After common carotid artery reperfusion | Mild therapeutic hypothermia (33 °C) |
During the ischemia | 2 hours | Additive or synergistic | ↓Infarction volume ↓Apoptosis ↑Angiogenesis ↓Glial scar formation ↓Inflammatory responses |
| Mu et al. [43] (2019) |
MCAO in rats | hADMSCs | 2 × 106 cells, intravenously | 2 or 7 days after MCAO | Enriched environment | 2 days after MCAO | 42 days | Overlapping or additive | →Infarction volume →Angiogenesis →Glial scar formation |
MCAO: middle cerebral artery occlusion; hESC: human embryonic stem cell; NPCs: neural progenitor cells; mSVZ: mouse subventricular zone; dMCAO: distal middle cerebral artery occlusion; hASCs: human adipose stem cells; rMSCs: rat mesenchymal stem cells; rADSCs: rat adipose-derived stem cells; hADMSCs: human adipose-tissue-derived mesenchymal stem cells; n.a.: not applicable; ↑: up-regulation; ↓: down-regulation.