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Table 1 Notable results from a selection of preclinical experiments treating SOD1 G93A rodent models of amyotrophic lateral sclerosis with mesenchymal stem cells

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   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%   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)  
(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)
  1. All listed percentage changes were found to be significant by the original authors. Changes are compared with sham, vehicle control, or untreated subjects unless otherwise noted. ALS, amyotrophic lateral sclerosis; BBB, Basso Beattie Bresnahan; BDNF, brain-derived neurotrophic factor; ChAT, choline acetyltransferase; GDNF, glial cell line-derived neurotrophic factor; GFAP, glial fibrillary acidic protein; GLP1, glucagon-like peptide 1; hMSC, human mesenchymal stem cell; IGF, insulin-like growth factor; mMSC, mouse mesenchymal stem cell; MN, motor neuron; MSC, mesenchymal stem cell; Ngn1, neurogenin 1; NMJ, neuromuscular junction; rMSC, rat mesenchymal stem cell; VEGF, vascular endothelial growth factor.