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| Reference | Cell type | Route | Dose, infusion volume, rate, and timing | Animals | Model | Engraftment | Functional outcome | Cellular/molecular effects |
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| Zhang et al., 2006 [30] | Rat BM-MSC | IA (carotid artery), IV (cervical vein), or ICV | 2 × 106 cells in 20 µL saline, slowly injected on days 1, 3, 5, and 7 after ICH | Sprague-Dawley rats weighing 270–300 g | Injection of 0.5 U collagenase VII into the left striatum (caudate nucleus) | BrdU-labeled cells found around the bleeding focus, in the ipsilateral cortex and ipsilateral hippocampus (except in the IV group), on days 1, 3, 5 and 7 after injection | Improved (beam balance test), on days 1, 3, 5, and 7 after injection (IA and ICV groups only). | NA |
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| Seyfried et al., 2006 [27] | Human BM-MSC | IV (tail vein) | 3 × 106, 5 × 106, or 8 × 106 cells in 1 mL PBS, slowly injected 1 day after ICH | Male Wistar rats weighing 270–320 g | Injection of 100 µL autologous whole blood into the right striatum | Human cells were detected by the mAb 1281; cells were found in the injured region (14 days after ICH) | Improved in all groups (NSS and corner turn test), 7 and 14 days after ICH | Decreased striatal tissue loss (all tested doses); increased neurogenesis and synaptogenesis |
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| Seyfried et al., 2008 [28] | Human BM-MSC | IA (internal carotid artery);
IV injection of mannitol (1.5 g/kg) alone or 10 min before IA injection of BM-MSC | 1 × 106 cells in 100 μL PBS, 1 day after ICH | Male Wistar rats weighing 270–320 g | Injection of 100 µL autologous whole blood into the right striatum | Human cells were detected by the mAb 1281; more cells were found in the injured region in the IA BM-MSC + IV mannitol group (14 days after ICH) | Improved only in the IA BM-MSC + IV mannitol group (NSS and corner turn test), up to 14 days after ICH | Decreased striatal tissue loss; increased neurogenesis and synaptogenesis; improvements occurred only in the IA BM-MSC + IV mannitol group |
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| Otero et al., 2010 [36] | Rat BM-MSC | IC (into the injured zone) | 2 × 106 cells in 10 μL of saline, 3 days after ICH | Female Wistar rats weighing 200–250 g | Injection of 0.5 U collagenase IV into the striatum | BrdU-labeled cells and male (donor-derived) cells found near the lesion (1 month after transplantation) | Improved (Rotarod and mNSS), 3 and 4 weeks after ICH | Increased number of proliferating cells (Ki67+) in the SVZ |
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| Seyfried et al., 2010 [29] | Rat BM-MSC | IV (tail vein) | 0.5 × 106 or 1 × 106 cells in 1 mL PBS, 1 day after ICH | Female Wistar rats weighing 270–320 g | Injection of 0.1 cc of blood into the right striatum | Y chromosome-positive cells (donor-derived) found in the ipsilateral hemisphere (14 days after ICH) | Improved only in the group that received the higher dose (NSS and corner turn test), 7 and 14 days after ICH | Decreased striatal tissue loss (2 weeks after ICH); increased neurogenesis and synaptogenesis; improvements occurred only in the high-dose group |
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| Yang et al., 2011 [61] | Rat BM-MSC or rat BM-MSC overexpressing GDNF | IC (into the right striatum) | 5 × 105 cells in 20 μL saline, injected at 2 mL/min, 3 days after ICH | Wistar rats weighing 270–320 g | Injection of 0.25 U collagenase I into the right striatum | GFP-positive cells found mainly in the area surrounding the injection site (up to 2 weeks after transplantation) | Improved in both groups, but GDNF-BM-MSC improved further (mNSS), up to 2 weeks after ICH | Decreased lesion volume and decreased number of apoptotic cells in the striatum in both groups, but better results were obtained in the GDNF-MSC group; increased GDNF protein levels in the ipsilateral striatum (only in the GDNF-MSC group) |
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| Otero et al., 2011 [34] | Rat BM-MSC | IC (into the injured zone) | 5 × 106 cells in 15 μL of saline, 2 months after ICH | Adult female Wistar rats | Injection of 0.5 U collagenase IV into the striatum | Y chromosome-positive cells found in the vicinity of the lesion (six months after cell transplantation) | Improved (mNSS, Rotarod, and locomotor activity), up to 6 months after treatment | No change in the number of proliferating cells (Ki67+) in the SVZ |
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| Feng et al., 2011 [32] | Human BM-MSC | IC (into 9 points near the hematoma) | 1–5 × 106 cells in 250 µL of vehicle, 1 or 4 weeks after ICH | Male Macaca fascicularis monkeys weighing 4.2 ± 0.2 kg (4–6 y old) | Injection of 1.5 mL of blood between the right cortex and the basal ganglia (outside the right putamen) | NA | Improved in both the early and late treatment groups (neurologic deficit score), up to 8 weeks after treatment | Increased 18F-fluorodeoxyglucose uptake (better results were obtained in the early treatment group); increased microvessel density in the region surrounding the hematoma in both groups |
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| Otero et al., 2012 [33] | Rat BM-MSC | IC (into the injured zone) | 2 × 106 cells in 15 μL of saline, 2 hours after ICH | Female Wistar rats, weighing 200–250 g | Injection of 0.5 U collagenase IV into the striatum | Y chromosome-positive cells found in the vicinity of the lesion (up to 28 days after ICH) | NA | Increased number of proliferating cells (Ki67+) in the SVZ; decreased number of apoptotic cells in the lesion zone |
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| Khalili et al., 2012 [22] | Rat BM-MSC | IV (tail vein) | 3 × 106 cells in 1 mL PBS, 1 day after SAH | Female Wistar rats weighing 275–300 g | Injection of 0.3 mL of blood into subarachnoid space | BrdU-positive cells were detected in the parietal lobe (14 days after SAH) | Improved (NSS), 14 days after SAH | Decreased number of apoptotic cells in the brain |
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| Wang et al., 2012 [23] | Rat BM-MSC | IV (tail vein) | 1 × 106 cells in 1 mL PBS, 1 hour after ICH | Male Sprague-Dawley rats weighing 270–320 g (12 weeks old) | Injection of 0.4 U collagenase VII into the striatum | NA | Improved (mNSS), 7, 14, 21, and 28 days after ICH | Decreased hemorrhage volume; increased number of proliferating cells and decreased number of apoptotic cells in the perihematomal region; upregulated the expression of antiapoptotic molecules, G-CSF, and BDNF |
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| Liang et al., 2013 [62] | Rat BM-MSC | IC (into 3 injection sites) | 3 injections of 1 × 106 cells in 10 µL PBS each, 1 day after ICH | Male Wistar rats weighing 250–300 g (4 months old) | Injection of 0.8 U collagenase IV into the striatum | PKH26-labeled cells found in the lesion site, corpus callosum, and hippocampus (35 days after ICH) | Improved (modified limb placing test and vibrissae-elicited forelimb placing test), up to 28 days after ICH | No change in hemispheric atrophy; increased density of fibers crossing the midline; increased neuronal plasticity |
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| Vaquero et al. 2013 [35] | Rat BM-MSC | IC (into the injured zone); one group received the cells embedded in a PRP scaffold | 5 × 106 cells in 30 µL vehicle, injected over 5 min, 2 months after ICH | Female Wistar rats weighing 200–250 g | Injection of 0.5 U collagenase IV into the right striatum | Y chromosome-positive cells were found near the lesion and next to the SVZ; more cells were detected in the BM-MSC + scaffold group (6 months after cell transplantation) | Improved in both groups, but better results were obtained in the BM-MSC + scaffold group (Rotarod and locomotor activity test), up to six months after treatment | No significant change in lesion volume; increased number of proliferating cells (Ki67+) in the lesion zone (only in the BM-MSC + scaffold group) and in the SVZ (in both groups: BM-MSC alone or BM-MSC + scaffold) |
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| Bao et al., 2013 [24] | Flk-1+ human BM-MSC | IC (into 3 injection sites) | 2 × 105 cells in 15 μL of saline, 1 day after ICH | Male Sprague-Dawley rats weighing 190–210 g | Injection of 0.4 U collagenase VII into the striatum | Human cells were detected by the mAb 1281; cells were found close to the hemorrhagic boundary zone (55 days after transplantation) | Improved (mNSS), up to 56 days after ICH | Decreased brain water content; no significant change in hemorrhage volume; decreased number of microglia/macrophages and neutrophils in the hemorrhagic boundary; induced angiogenesis in the hemorrhagic boundary; decreased number of apoptotic cells and increased number of neurons in the hemorrhagic boundary; downregulated expression of several cytokines in the brain |
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| Khalili et al., 2014 [67] | Rat BM-MSC | IV (tail vein) | 3 × 106 cells in 1 mL PBS, 1 day after SAH | Female Wistar rats weighing 275–300 g | Injection of 0.3 mL of blood into subarachnoid space | NA | NA | Improved ultrastructural morphology |
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| Wang et al., 2015 [31] | Rat BM-MSC | IV (tail vein) | 1 × 106 cells in 100 μL vehicle | Male spontaneously hypertensive rats | Injection of 50 μL of blood into the striatum | PKH26-labeled cells were found in the brain (up to 42 days after ICH, although the number of cells decreased over time) | Improved (mNSS and modified limb placing test), up to 42 days after ICH | Increased expression of occludin in the brain |
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| Sun et al., 2015 [37] | Hypoxia-preconditioned rat BM-MSC | Intranasal (30 min after the intranasal administration of 100 U hyaluronidase dissolved in PBS) | 1 × 106 cells in 100 μL vehicle, 3 and 7 days after ICH | Male C57BL/6 mice weighing 25–28 g (8–10 weeks) | Injection of 0.15 U collagenase
IV into the striatum | Hoechst 33342-labeled cells found in the olfactory bulb, ipsilateral cortex, perivascular spaces, and perihematomal regions (6 hours after transplantation) | Improved (mNSS, open field behavioral monitoring, Rotarod, and adhesive removal test), 14–21 days after ICH | Decreased tissue loss and ventricle enlargement; increased expression of GDNF, VEGF, and BDNF in the brain; increased SVZ neurogenesis |
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| Chen et al., 2015 [25] | Rat BM-MSC | IV (jugular vein) | 5 × 106 in 200 μL PBS injected over 10 min, 2 hours after ICH | Male Sprague-Dawley rats weighing 250–300 g | Injection of 0.5 U collagenase
IV into the striatum | NA | Improved (mNSS), 3 days after ICH | Decreased brain water content; decreased number of apoptotic cells in the cortical hemorrhagic boundary; decreased number of microglia/macrophages and neutrophils in the brain; decreased blood-brain barrier dysfunction; decreased the expression of proinflammatory cytokines, MMP9, iNOS, and 3-nitrotyrosine in the brain; increased expression of anti-inflammatory cytokines and TSG-6 in the brain; suppressed activation of the NF-κB signaling pathway |
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| Suda et al., 2015 [26] | Autologous rat BM-MNC | IV (tail vein) | 1 × 107 cells/kg in 1 mL PBS infused over 5 min, 1 day after ICH | Male Long Evans rats weighing 275–325 g or retired breeder aged rats weighing 600–650 g | Injection of 70 μL of blood into the striatum | Qtracker-labeled cells found in the brain, spleen, lungs, liver, and kidney (6 and 24 hours after transplantation) | Improved both in young and in aged rats (Staircase test, 28 days after ICH, and Morris water maze test, 4 weeks after ICH) | Decreased brain water content and brain atrophy both in young and in aged rats; stimulated angiogenesis and SVZ neurogenesis; decreased number of degenerating neurons, iNOS-positive cells, and neutrophils in the perihematomal area; decreased expression of HMGB1, MMP9, S100β, and aquaporin 4 in the brain; decreased levels of the proinflammatory cytokine interleukin-1β in the serum |
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