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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