TABLE 2.

Preclinical studies of human cells in rodent models.

Cell Type	Cell Source	Rodent Model	Intervention	Cell Doses (cells)	Results	Ref
iPSCs	hiPSCs	90-day-old SOD1G93A mice	Intraspinal	8 × 104	Differentiation of astrocytes and prolonged lifespan without tumorigenic formation	Kondo et al. (2014)
iPSCs	hiPSCs	90/105/120-day-old SOD1G93A mice	Intrathecal/intravenous	1 × 106	Improved neuromuscular function and survival, neuroprotection, and positive host-environment modifications	(Nizzardo et al., 2014)
iPSCs	hiPSCs	90-day-old SOD1G93A mice	Intrathecal	1 × 106	Increased survival and improved neuromuscular phenotype	Nizzardo et al. (2016)
iPSCs	hiPSCs	3-month-old SOD1G93A rats	Intraspinal	1 × 105	Successful survival and differentiation into mature neurons	Popescu et al. (2013)
MSCs	hUCMSCs	98-day-old SOD1G93A mice	Multiple intracerebroventricular injections	2.5 × 105	No transplanted cells migrate to the spinal cord, a partial but significant protection of MNs was detected (anti-inflammatory, neuroprotective) in the lumbar spinal cord. Did not prevent muscle denervation nor delayed disease progression	Sironi et al. (2017)
MSCs	hADMSCs	8-week-old SOD1G93A mice	Intraperitoneally	1 × 106	No significant difference was observed in the survival of mice treated with MSCs	Coatti et al. (2017)
MSCs	hBMMSCs	SOD1G93A rats	Intrathecal	5 × 105	Ameliorated disease progression, significantly improved motor activity, prolonged survival	Forostyak et al. (2014)
MSCs	hBMMSCs	SOD1G93A mice	Intravenous	1 × 106	MSCs-Ngn1 delayed disease onset, enhanced motor functions and can migrate to the CNS	Chan-Il et al. (2013)
MSCs	hBMMSCs-GDNF	SOD1G93A rats	Intramuscular	1.2 × 105	Ameliorate motor neuron loss, delayed disease progression, increased overall lifespan by up to 28 days	Suzuki et al. (2008)
MSCs	hBMMSCs	mdf/ocd mutant mice	Intrathecal	5 × 105	Ameliorating the symptoms of a motor neuron degenerative mouse model and a less degree of MSCs improved significantly in the motor tests performed	Boucherie et al. (2009)
MSCs	hBMMSCs	2-month-old SOD1G93A mice	Cisterna lumbaris injection	3 × 105	Motoneuron death and motor decay were delayed, astrogliosis was reduced, and microglial activation was modulated	Boido et al. (2014)
NSCs	hNSCs	62-day-old SOD1G93A rats	Lumbar puncture	4 × 105	Prolonged lifespan, delayed motor neuron death, disease onset, and progression	Xu et al. (2006)
NSCs	hNSCs	56-day-old SOD1G93A rats	Lumbar puncture	1.6 × 105	Advanced degree of structural integration between grafted cells and host ones, prolonged lifespan, delayed motor neuron death, disease onset, and progression	Xu et al. (2009)
NSCs	hNSCs-VEGF	70-day-old SOD1G93A mice	Intrathecal	1 × 105	Delayed disease onset, prolonged survival, provided neuroprotective effect	Hwang et al. (2009)
NSCs	hNSCs	63-day-old SOD1G93A rats	Laminectomy	2.4 × 105	Prolonged lifespan, extended disease duration, delayed disease onset, attenuated motor weakness	Xu et al. (2011)
NSCs	hNSCs	60–65-day-old SOD1G93A rats	Laminectomy	1 × 105	Transient local improvement of MNs, no survival benefit, no delayed onset/progression	Hefferan et al. (2012)
NSCs	hNSCs	8-week-old SOD1G93A rats	Lumbar puncture	8 × 104	Stimulate endogenous neurogenesis, initiate intrinsic repair mechanisms	Xu et al. (2012)
GPCs	hGPCs	70-day-old SOD1G93A rats	N/A	1.456 × 106	Increased motor neuron survival, no effect on the loss of muscle innervation	Suzuki et al. (2007)
GPCs	hGPCs	75-day-old SOD1G93A mice	N/A	N/A	Attenuated the loss of MNs, induced trophic changes in MNs, no improvement in motor performance and extension of lifespan	Park et al. (2009)
GPCs	hGPCs	50–60-day-old SOD1G93A mice	Laminectomy	2 × 105 6 × 105	No motor neuron protection or any therapeutic benefits	Lepore et al. (2011)
GPCs	hGPCs	80-day-old SOD1G93A rats	Laminectomy	4 × 105	Delayed disease onset, extended survival, improved health of MNs	Thomsen et al. (2018)
UCBCs	hUCBCs	5∼6-week-old SOD1G93A mice	N/A	1 × 108	Improved probability of neuromuscular transmission	Souayah et al. (2012)
UCBCs	hUCBCs	22–25-week-old SOD1G93A mice	N/A	1 × 106	UCBCs transfected with VEGF and ${\text{L}}_1$ CAM differentiated into endothelial cells, formed new blood vessels and secreted neuro-trophic factors, supporting neurogenesis	Rizvanov et al. (2008)
UCBCs	hUCBCs	8-week-old SOD1G93A mice	N/A	3.42–3.56 × 106	Considerably delayed onset of symptoms and death	Ende et al. (2000)
UCBCs	hUCBCs	7∼8-week-old SOD1G93A mice	Intravenous	1 × 107 2.5 × 107 5 × 107	Increased lifespan, delayed disease progression, decreased proinflammatory cytokines in the brain and spinal cord, higher response of splenic cells to mitogens, significantly increased lymphocytes and decreased neutrophils in the peripheral blood, stable reduction in microglia density in both cervical and lumbar spinal cords	Garbuzova-Davis et al. (2008)
UCBCs	hUCBCs	45-day-old SOD1G93A mice	Intrathecal	1 × 105	Narrowed therapeutic effects due to limited intraparenchymal migration and survival	Habisch et al. (2007)
UCBCs	hUCBCs	9/13-week-old SOD1G93A mice	Intravenous	1 × 106 2.5 × 106	Delayed functional deterioration, increased lifespan, higher motor neuron counts, reduced astrocytes and microglia	Garbuzova-Davis et al. (2012)
UCBCs	hUCBCs	29-week-old SOD1G93A mice	Intravenous	2 × 106	Increased life span and performance in behavioral tests	Islamov et al. (2017)