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 | |
|  | 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 | |
|  | 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 | |
|  |  | 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 | |
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 | |
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 | |
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 | |
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 | |
|  | 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 |
