Table 2. Veterinary clinical stem cell trials in neurologic disease.
| Disease | Cell therapy | No. of dogs | Control | Evaluation periods/effects | Ref. |
|---|---|---|---|---|---|
| SCI (T3-L7) | Autologous NIBM-MSCs; intra spinal injection; 5.0 × 106 cells for 2 times with a 21-day interval. | 13 dogs in stem cell group | No | At 2, 5, 7, and 12 months; improvement in gait score in 6 of the cases, and improvement in proprioception and nociception in 2 cases | [58] |
| SCI | Autologous NIBM-MSCs; intra spinal injection; 5.0 × 106 cells 2 times with a 21-day interval. | 7 dogs in stem cell group | No | At 2, 4 and 8 months; some beneficial effect of intraspinal injection of autologous NIBM-MSCs in dogs with paraplegia | [59] |
| SCI (T10-L4) | Autologous olfactory mucosal cells; intraspinal transplant; 6.24 × 106 cells | 23 in stem cell group; 11 in control group (received cell transport medium alone) | Yes | At 1, 3 and 6 months; no evidence for concomitant improvement in long tract function | [60] |
| Severe SCI (T11-L2) | Autologous olfactory glial cells; intraspinal transplant; 5 × 104 cells | 8 dogs in stem cell group | No | From 2 months to 1 year; the transplantation procedure itself is non-injurious and feasible; beneficial effect on locomotion | [61] |
| SCI | Allogenic AD-MSCs; intra spinal injection; 1 × 107 cells | 9 dogs in surgery and stem cell group; 25 dogs in surgery group | Yes | Follow-up more than 6 months; better recovery outcomes compared to decompression surgery alone | [62] |
| Severe acute SCI (T6-L5) | Autologous BM stromal cells; IT into the CSF; 1.0 × 106 cells to 6 × 106 cells (mean, 3 × 106 cells) 3 times at 1-week intervals | 7 dogs in stem cell group | No | Follow-up until 29-62 months after SCI; there were no complications; Only 2 of 7 dogs regained the ability to walk, no changes in sensory function | [63] |
| SCI (T13-L7) | Autologous BMSCs; intraspinal transplant (intraparenchymal); 1 × 106 cells in each 1 cm3 of lesion | 4 dogs in stem cell group | No | At 100 days, 12 months and 18 months; faster clinical recovery and improved movement in 3 of the 4 dogs; no changes in magnetic resonance imaging | [65] |
| Severe SCI (T11-L4) | Autologous BM-MNCs; subarachnodal to the lesioned spinal cord; 4.5 × 106 to 2.3 × 109 cells (mean, 8.88 × 107 cells) | 36 dogs in stem cell group; 46 dogs in control group | Yes | Ambulatory recovery rate was assessed (mean time of ambulatory recovery was 34.84 days); significant increase in the recovery rate was revealed | [66] |
| Chronic SCI | Autologous BMSCs; IT into the cerebrospinal fluid; 0.3 × 105 cells to 3 × 106 cells (median, 1.3 × 106 cells) 3 times at 1-week intervals | 10 dogs in stem cell group; 13 dogs in control group | Yes | At 1, 2, 3, 4, 5, and 6 months, until 6-35 months; there were no complications; improvement of pelvic limb locomotor function | [64] |
| Meningoencephalomyelitis of unknown origin | Autologous BMSCs; IT in the cisterna magna (2.0 × 106 cells), IV (0.5 × 106 cells), and IA in the right carotid artery (4.0 × 106 cells) | 8 dogs in stem cell group (3 in IT + IA, 4 in IT + IV, 1 in IT + IA after IT + IV) | No | For 6 months up to 2-year follow-up; No major short- or long-term adverse effects; early improvement in general and neurological conditions, IT + IA group showed a shorter time of reaction to therapy | [78] |
| Fibrocartilaginous embolic myelopathy | hUCB-MSCs; percutaneous transplantation into parenchyma; 1.0 × 106 cells | 1 dog | No | At 12 weeks; locomotor functions improved following transplantation. | [68] |
SCI, spinal cord injury; NIBM-MSC, neurogenically-induced bone marrow-derived mesenchymal stem cell; IV, intravenous; IA, intra-arterial; IT, intrathecal; AD-MSC, adipose tissue-derived mesenchymal stem cell; BM, bone-marrow; BM-MNC, bone marrow-derived mononuclear cell; BMSC, bone-marrow-derived mesenchymal stem cell; hUCB-MSC, human umbilical cord derived mesenchymal stem cell.