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Table 1 Summary of BM-MSC injections in ALS rodent model

From: Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis

ALS model   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 [58, 62]
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]
  1. hBM-MSC human bone marrow-derived mesenchymal stem cells, DMEM Dulbecco’s modified eagle medium, Ngn1 neurogenin-1, PBS phosphate buffered saline, mBM-MSC mouse bone marrow-derived mesenchymal stem cells, ALS-hBM-MSC human bone marrow-derived mesenchymal stem cells derived from ALS patient, ALS-CSF cerebrospinal fluid derived from ALS patient, GFP-hBM-MSC green fluorescent protein labelled hBM-MSC, PNN perineural net, BrdU bromodeoxyuridine, GDNF glial derived neural factor