Table 2.

Selection of clinical trials for neural applications carried out using injectable cell therapy

Cells	Application	Route of administration	Injection device	Cell dose	Volume injected	Flow rate	Outcome	Refs.
MSCs	Amyotrophic lateral sclerosis	Intraspinal	Syringe with 18 G cannula needle mounted on a table fixed arm with a micrometric system. Cannula pre-modified to inject upwards and downwards	110 × 106 cells. During treatment, different cell numbers were obtained in each subject. Only one patient received <15 × 106 cells	Cells suspended in about 1 mL of autologous CSF	Not stated	MSC transplantation into the spinal cord is safe, but no definitive conclusion about cell vitality after transplantation	119
	Parkinson’s disease	Direct transplantation into the midbrain	Each patient was mounted with a Leksell stereotactic headframe. A 50 μL Hamilton syringe, fitted with a custom-made microinjector. Cell suspension was deposited along each of four putaminal trajectories	Final cell concentration of ≈80,000/μL. Total of 3.2 × 106 cells in one patient and about 4.8 × 106 cells in the other	E.g.: In the first patient, 40 μL injected along four tracks in the right postcommissural putamen, and 32 μL in the left	Not stated	Results demonstrate that such therapies can be effective in some patients at advanced stages of disease. Changes in methodology may result in better clinical outcome	46
	Chronic spinal cord injury	Intraarterial	Cobra 2 catheter (tubular, polyurethane 4 Fr and 65 cm long)	2.5 × 106 CD 34+ cells/kg	Not stated	10 mL/min	Recovery of somatosensory evoked response to peripheral stimuli in 67% of patients. During a 2.5-year follow-up, this protocol proved safe	120
		Intrathecal	Not stated	5 × 106 to 10 × 106/kg of mononuclear cells	Not stated	Not stated	No statistical improvement demonstrated. One case of encephalomyelitis after 3rd injection. 24 patients developed neuropathic pain	27
LBS-neurons	Ischaemic or haemorrhagic stroke	Intracerebral	0.9 mm-OD cannula with 20 µL. Cells were aspirated into 100 µL syringe	5 × 106 or 1 × 107 cells	10 µL was injected slowly at each site over 2 mins	5 µL/min. Total time was around 150 min	A quantifiable improvement was noted in some patients but no evidence of significant value in motor function	4
MSCs and NSPCs	Ischaemic stroke	Either four IV injections of MSCs or one IV injection of MSCs followed by three injections of MSCs and NSPCs through the cerebellomedullary cistern	Not described	Either four IV injections of MSCs at 0.5 × 106/kg body weight; or one IV injection of MSCs at 0.5 × 106/kg followed by three injections at 5 × 106/patient and NSPCs at 6 × 106/patient	IV injections of MSCs in 250 mL saline; and the injections of MSCs and NSPCs in 10 mL saline	Not stated	No evidence of neurological deterioration, Infection or tumorigenesis at a 2-year follow-up. Neurological functions and disability levels were improved	39
NSI-566RSC (Neuralstem, Inc)	Amyotrophic lateral sclerosis	Intraspinal	Microinjection platform base attached to a custom self-retaining retractor system. Five sequential unilateral injections	1 × 104 cells/mL	5 injections of 10 µL at 4-mm intervals	Not stated	Delivery was well tolerated	121
Olfactory ensheathing cells	Complete, thoracic paraplegia	Intraspinal	25 µL Hamilton syringe with 28 G bevelled needle	80,000 cells/µL	Four injections of 1.1 µL during each penetration	Injections frame-assisted and freehand	Transplantations were feasible and safe up to 3 years post-implantation	43, 122
	Chronic thoracic paraplegia	Intraspinal	Automatic micropump and 3D micromanipulator, with 25 μL glass syringe and 26 G bevelled needle	30,000–200,000 cells/μL	Volume of single injections was 0.5 μL	2 μL/min	Neurological improvements in the three patients, with confirmation of significance requiring larger sample	42

This table is illustrative of the numerous clinical cell-therapy trials undertaken in the field of neurodegenerative diseases. Trials shown were selected to exemplify the range of therapies currently under investigation, and should not be taken as an indication of the quality of any particular trial.

IV Intravenous.