Table 1.
Stem cell technology utilization in motor neuron disease.
| Cell type | Model | Outcome | Ref. | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Species | Type | Modification | Species | Genetic modification |
Delivery; treatment age | Disease onset |
Survival increase |
Additional notes | |
| ALS | |||||||||
| Mouse | ES | MN differentiated | Rat | SOD1-G93A | Direct spinal implant; 10 weeks | None | None | Loss of grafted cells by end stage | [115] |
| Mouse | BM | N/A | Mouse | SOD1-G93A | Intraperitoneal injection; 4 weeks | Delay | 13 days | MN protection; differentiation into neurons and contribution to non-neuronal tissue | [83] |
| Mouse | BM | GFP tag | Mouse | SOD1-G93A | Intra-bone marrow transplantation; 12 weeks | None | ~10 days | No MN protection; GFP-positive cells in spinal cord; differentiation into glia; no neuronal differentiation | [86] |
| Mouse | BM | Lin-c-kit + specific cells | Mouse | SOD1-G93A | Intravenous injection; 70 days | 4-day delay | 17 days | MN protection, slowed progression; neuronal differentiation | [84] |
| Mouse | NPC | Le + CX + specific cells | Mouse | SOD1-G93A | Direct spinal implantation; 70 days | Delay | 23 days | MN protection; neuronal differentiation | [116] |
| Rat | Primary NPC | GFP | Rat | SOD1-G93A | Intravenous injection; 14, 26 weeks | N/A | N/A | NPC migration to the CNS and differentiation | [85] |
| Rat | GRP | N/A | Rat | SOD1-G93A | Direct spinal implantation; 90 days | None | 17 days | MN protection; astrocyte differentiation; decreased microgliosis | [16] |
| Human | UBC | N/A | Mouse | SOD1-G93A | Intravenous injection; 7–8 weeks | Delay | Various | Dose-dependent changes in survival; cytokine regulation | [88] |
| Human | UBC | N/A | Mouse | SOD1-G93A | Intravenous injection; 66 days | Delay | 2–3 weeks | Migration to the CNS; neuronal differentiation | [87] |
| Human | UBC | VEGF, FGF2 | Mouse | SOD1-G93A | Retro-orbital injection; 24–28 weeks | N/A | N/A | Migration to the CNS; differentiation to migroglia and astrocytes | [117] |
| Human | MSC | GDNF producing | Rat | SOD1-G93A | Intramuscular transplantation; 80 days | None | 28 days | Protection of MN in the spinal cord and NMJ integrity | [93] |
| Human | MSC | Derived from ALS patients | Mouse | SOD1-G93A | Injection into cisterna magna; 60 days | None | 7 days | Dose-dependent effect on survival; slowed progression | [118] |
| Human | NPC | VEGF producing | Mouse | SOD1-G93A | Intrathecal injection; 70 days | Delay | 12 days | Regulation of apoptosis pathway | [119] |
| Human | NPC | BDNF, IGF-I, VEGF, NT-3, GDNF | Mouse | SOD1-G93A | Injection into cisterna magna; 75 days | None | None | Astrocyte differentiation and MN protection with production of GDNF or IGF-I | [92] |
| Human | NPC | N/A | Rat | SOD1-G93A | Direct spinal implantation; 62 days | Delay | 10 days | Neuronal differentiation, MN protection, delayed progression, growth factor production | [4] |
| Human | NPC | N/A | Rat | SOD1-G93A | Direct spinal implantation; 56 days | N/A | N/A | Integration and formation of synaptic contacts between graft and host | [91] |
| Human | NPC | GDNF producing | Rat | SOD1-G93A | Direct spinal implantation; 90/100 days | None | None | [120] | |
| Human | NPC | GDNF producing | Rat | SOD1-G93A | Direct spinal implantation; 70 days | None | None | MN protection | [90] |
| SMA | |||||||||
| Mouse | ES | GFP, NPC differentiation | Mouse | Smn−/− SMN2+/+SMNΔ7+/+ | Intrathecal injection; 1 day | N/A | 6.75–8.17 days | Neural (including MN) and astrocyte differentiation, MN and NMJ protection, growth factor production, axon projection toward ventral root | [95] |
| Mouse | ES | HB9-GFP, ALDHhiSSClo specific, neural ‘primed’ | Mouse | Smn−/− SMN2+/+SMNΔ7+/+ | Intrathecal injection; 1 day | N/A | 5.12 days | Neural (including MN) and astrocyte differentiation, MN and NMJ protection. Growth factor production | [94] |
ALS: Amyotrophic lateral sclerosis; BDNF: Bone-derived neurotrophic factor; BM: Bone marrow; GDNF: Glial-derived neurotrophic factor; GFP: Green fluorescent protein; GRP: Glial restricted precursor; ES: Embryonic stem; MN: Motor neuron; MSC: Mesenchymal stem cell; N/A: Not applicable; NMJ: Neuromuscular junction; NPC: Neural progenitor cell; NT: Neurotrophin; UBC: Umbilical cord cell.