From: Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis
ALS model | Â | Delivery Method | Cell numbers | Age | Sacrifice to evaluate graft | Outcomes | Cell graft | Reference |
---|---|---|---|---|---|---|---|---|
SOD1 G93A mice | hBM-MSC after 5 passages in culture | Intravenous | 3 × 10 6 in 0.3 ml of L-DMEM | Pre-symptomatic (8 w) | 14 days post- injection | Increased lifespan of 18 days, delayed disease onset of 14 days and reduced motor neuron loss | Very few cells in grey and white matter of lumbar spinal cord. Considerable number of cells in kidney, lung and spleen. | [61] |
SOD1 G93A mice | hBM-MSC expressing Ngn1 after 5 passages in culture | Intravenous | 1 × 10 6 in 0.1 ml of PBS | Pre-symptomatic (8 w) or symptom onset (14–16 w) | 14 days post- injection | Increased lifespan of 3 days, delayed disease onset of 5 days and reduced motor neuron loss. | Very few cells in brainstem and spinal cord. Cells mostly found in kidney. | [58] |
SOD1 G93A mice | mBM-MSCs expressing Luciferase expanded for 8–15 passages | Intravenous | 1 × 10 6 in 0.2 ml of PBS | Symptom onset | 24 h, 3 weeks and 4 weeks post-Injection | Increased lifespan of 17 days, delayed decline in motor performance and weight loss. | Cells detected in spinal cord and hypothalamus after 24 h and 48 h. Very few cells after 20 days. No cells after 35 days | |
SOD1 G93A mice | hBM-MSC-derived neural-like cells from neurosphere | Cisterna Magna | 1x10 5 in 10 μl of PBS | Pre-symptomatic | 10 days post-injection | No benefits | Subarachnoid space near cisterna magna and within cerebellum. | [63] |
SOD1 G93A mice | ALS-hBM-MSC after 3 passages in culture | Cisterna Magna | 1 x 10 6 in 10 μl of ALS-CSF | Pre-symptomatic | 7 weeks post-injection | Increased lifespan of 8 days, slowed decline in rotarod test and increased motor neuron survival | Ventricular system and subarachnoid space. Some cells into brain and spinal cord. | [64] |
SOD1 G93A mice | hBM-MSC after 3–4 passages in culture | Cisterna Magna | 5 × 10 5 in 5 μl of PBS | Pre-symptomatic | 3 weeks post-injection | Increased lifespan of 14 days, delayed disease onset of 6 days and reduced astrogliosis | Not shown | [67] |
SOD1 G93A rats | GFP-hBM-MSCs | Cisterna Magna | 5x10 5 in 10 μl of PBS | Symptom onset | 14 days post-injection | Increased lifespan of 14 days and reduced motor neuron loss. Preservation of PNN. | No graft | [66] |
SOD1 G93A rats | BrdU-labelled mBM-MSC after 15 passages in culture | Cisterna Magna | 2 x 10 6 in 15 μl of Opti-MEM | Symptom onset | 35 days post-injection | Increased lifespan of 16 days, slowed disease progression, reduced motor neuron loss and inflammation. | White and grey matter of spinal cord. Substantial differentiation into astrocyte phenotype | [54] |
SOD1 G93A mice | Bisbenzimide -hBM-MSC after 3–8 passages in culture | Cisterna lumbaris (L5-L6) | 3 × 10 5 in 5 μl of PBS | Symptom onset | 14 days post- injection | Reduced astrogliosis and microglial activation. | Lumbar, cervical and thoracic meninges. Migration into spinal cord parenchyma. | [68] |
SOD1 G93A mice | Bisbenzimide -hBM-MSC after 3–5 passages in culture | Intraspinal (L1-L2) | 1 × 10 5 in 2 μl of PBS | Pre-symptomatic (28 w) | 10 weeks post- injection (38 w) | Reduced astrogliosis and microglial activation. Improved motor function and delayed neuron death | Close to injection site. Migration up to 2 mm toward ventral horn. | [70] |
SOD1 G93A rats | GFP-hBM-MSC engineered to secrete GDNF | Intramuscular after focal injuries | 1.3 × 10 5 in | Pre-symptomatic (80 days) | Disease end-point | Prolonged survival, reduction in denervated motor endplates and reduced motor neuron loss | Between basal lamina and muscle fibres | [72] |