From: Therapeutic applications of mesenchymal stem cells for amyotrophic lateral sclerosis
Model and species | Cell type | Treatment route | Treatment timing | Clinical effects | Life-span effects | Post-mortem observations of MSCs and MNs | Other effects | Reference |
---|---|---|---|---|---|---|---|---|
SOD1G93A mouse | hMSC | Intraspinal (105) | Pre-onset (week 28) | Significantly improved motor score and rotarod performance in treated males (week 32) | Not assessed | MSCs survived in spinal cord | 36% decrease in number of CD11b+ microglia | Vercelli et al. [48] (2008) |
54% increase in MNs in treated females (week 38) | 45% decrease in number of GFAP+ astrocytes (week 38) | |||||||
SOD1G93A rat | rMSC | Intrathecal lumber spinal cord (2 × 106) | Disease onset (week 13) | 12% delay in paralysis onset | 13% increase | MSCs survived in spinal cord 71% increase in number of lumbar MNs (week 18) | 62% decrease in number of CD11b+ microglia (week 18) | Boucherie et al. [21] (2009) |
SOD1G93A mouse | hMSC from patient with ALS | Intrathecal (A) 104 | Pre-onset (week 8) | (A, B) No significant difference in motor performance | (A) No significant change | MSCs detected in ventricular system, subarachnoid space, brain, spinal cord | No significant difference in disease onset | Kim et al. [54] (2010) |
(B) 2 × 105 | ||||||||
(B) 4.7% increase | ||||||||
(C) 106 | ||||||||
(C) Significantly delayed decline in rotarod performance | (C) 6.5% increase | |||||||
(A) No significant change in number of MNs | ||||||||
(B) 41% increase in | ||||||||
number of MNs | ||||||||
(C) 79% increase in number of MNs (week 15) | ||||||||
SOD1G93A mouse | Encapsulated hMSC-GLP1 | Intracerebro-ventricular | Pre-onset (week 5) | Significantly delayed disease onset and weight loss | 11% increase | Capsules not detected | Â | Knippenberg et al. [55] (2012) |
(2.5-3 × 103) | ||||||||
No significant change in MN count | ||||||||
Significantly delayed decline in rotarod performance | ||||||||
SOD1G93A rat | rMSC | Intraspinal (105) and intravenous (2 × 106) | Disease onset (week 16) | Significant BBB test and grip strength difference starting 4 weeks post-injection | 6.1% increase | MSCs survived in spinal cord |  | Forostyak et al. [20] (2011) |
55% increase in number of thoracic MNs | ||||||||
37% increase in number of lumbar MNs (end stage) | ||||||||
SOD1G93A mouse (irradiated) | hMSC | Intravenous (3 × 106) | Pre-onset | 9.0% delay in disease onset | 9.8% increase | MSCs detected in brain, brainstem, and spinal cord throughout disease progression |  | Zhao et al. [60] (2007) |
(week 8) | ||||||||
3-week delayed decline in rotarod performance | ||||||||
23% increase in number of lumbar MNs (week 16) | ||||||||
45% increase in number of lumbar MNs (week 20) | ||||||||
SOD1G93A mouse | (A) hMSC | Intravenous (106) | Pre-onset (week 8) | (2B, 3B) Improved motor performance week 16 | (3B) 7.3% increase | (1A, 1B) MSCs detected in spinal cord (week 10) (1A) No change in MN number (1B) 57% | Â | Chan-Il et al. [25] (2013) |
(1A, 1B, 2A, 2B, 3A) No significant effect | ||||||||
increase in number of cervical MNs, 50% increase in number of lumbar MNs (week 16) | ||||||||
(B) hMSC-Ngn1 | ||||||||
Disease onset (week 14–16) | ||||||||
Disease onset (weeks 13 and 15) | ||||||||
SOD1G93A mouse | mMSC | Intravenous (106) | Disease onset (week 12) | Significantly delayed decline in motor performance (rotarod, extension reflex, gait impairment) | 15% increase | MSCs detected in spinal cord at 24–48 hours with decreasing numbers over time | 24% decrease in ubiquitin+ cells | Uccelli et al. [61] (2012) |
16% decrease in GFAP+ astrocytes | ||||||||
34% decrease in IB4+ microglia | ||||||||
No significant change in MN count | ||||||||
(spinal cord, week 17) | ||||||||
Significantly increased body weight (week 16 onward) | ||||||||
SOD1G93A rat | (A) hMSC | Intramuscular (1.2 × 106 per time point) | Pre-onset once/week for 3 weeks | (A, B) Significantly slower motor dysfunction progression (measured by BBB test score) | (A) No significant change | MSCs survived in muscle | (A) No significant effect on NMJ innervation or denervation | Suzuki et al. [12] (2008) |
(B) hMSC-GDNF | ||||||||
(B) 17% increase | (A) 28% increase in number of ChAT+ lumbar MNs | |||||||
(weeks 11–13) | ||||||||
(B) Significantly Increased NMJ innervation and decreased denervation (week 17) | ||||||||
(B) 36% increase in number of ChAT+ lumbar MNs (week 17) | ||||||||
SOD1G93A Rat | (A) hMSC | Intramuscular (1.5 × 106 per time point) | Pre-onset once/week for 3 weeks | (C, F) 5% delay in disease onset | (B) 10% increase | (A-F) MSCs survived in muscle | (B, C, F) Significantly increased NMJ innervation | Krakora et al., 2013 [42] |
(B) hMSC-GDNF | ||||||||
(C) hMSC-VEGF | (A, B, D, E) No significant effect on onset | (C) 7.5% increase | (A) No significant change in number of large lumbar MNs | |||||
(weeks 12–14) | ||||||||
(F) Significantly increase NMJ innervation compared with (B, C) (week 21) | ||||||||
(D) hMSC-IGF-1 | ||||||||
(A, D, E) No significant change | ||||||||
(F) Significantly slower motor dysfunction progression (measured by BBB test score) | Â | |||||||
(E) hMSC-BDNF | ||||||||
(F) 16% increase | (B) 200% increase in number of large MNs | |||||||
(C) 150% increase in number of large MNs | ||||||||
(F) hMSC-GDNF/VEGF | ||||||||
 |  |  |  |  |  | (F) 230% increase in number of large MNs (week 21) |