Stable Intracerebral Transplantation of Neural Stem Cells for the Treatment of Paralysis Due to Ischemic Stroke

Abstract

NSI‐566 is a stable, primary adherent neural stem cell line derived from a single human fetal spinal cord and expanded epigenetically with no genetic modification. This cell line is being tested in clinical trials in the U.S. for treatment of amyotrophic lateral sclerosis and spinal cord injury. In a single‐site, phase I study, we evaluated the feasibility and safety of NSI‐566 transplantation for the treatment of hemiparesis due to chronic motor stroke and determined the maximum tolerated dose for future trials. Three cohorts (n = 3 per cohort) were transplanted with one‐time intracerebral injections of 1.2 × 107, 2.4 × 107, or 7.2 × 107 cells. Immunosuppression therapy with tacrolimus was maintained for 28 days. All subjects had sustained chronic motor strokes, verified by magnetic resonance imaging (MRI), initiated between 5 and 24 months prior to surgery with modified Rankin Scores [MRSs] of 2, 3, or 4 and Fugl‐Meyer Motor Scores of 55 or less. At the 12‐month visit, the mean Fugl‐Meyer Motor Score (FMMS, total score of 100) for the nine participants showed 16 points of improvement (p = .0078), the mean MRS showed 0.8 points of improvement (p = .031), and the mean National Institutes of Health Stroke Scale showed 3.1 points of improvement (p = .020). For six participants who were followed up for 24 months, these mean changes remained stable. The treatment was well tolerated at all doses. Longitudinal MRI studies showed evidence indicating cavity‐filling by new neural tissue formation in all nine patients. Although this was a small, one‐arm study of feasibility, the results are encouraging to warrant further studies. Stem Cells Translational Medicine 2019;8:999–1007

Brain morphological and connectivity changes on MRI after stem cell therapy in a rat stroke model

“…Our results are in line with MRI data from our previous clinical study, which showed atrophy within peri-infarct areas and secondary dilations of the adjacent ventricle were less prominent in MSC-treated patients than in control patients [ 48 ]. A recent small study showed cavity-filling by new neural tissue formation in patients who received intracerebral injection of a neural stem cell line [ 49 ]. Jiang and colleagues used DTI techniques to measure white matter recovery after stem cell therapy in a rat stroke model [ 22 ], and Chen and colleagues undertook a stem cell therapy clinical study and showed that DTI fiber number asymmetry scores were correlated with functional recovery, and were reduced in patients who received stem cells [ 50 ].…”

Clinical diagnostic and therapeutic guidelines of stroke neurorestoration (2020 China version)

“…(2) Cell therapy, such as intravenous or arterial injection of monocytes cells and mesenchymal stromal cells [38][39][40][41][42][43][44][45][46][47], injection of olfactory ensheathing cells (OECs) into olfactory sub-mucosa [48], and neural stem cells injection around the diseased region [49][50][51], is suitable for patients with stroke with mild, moderate, and severe neurological damage. Recent studies on high-level evidence-based medicine did not show the neurorestorative capability of mesenchymal stem cells for stroke during the recovering phase.…”

The 2019 yearbook of Neurorestoratology

“…Levy et al [14] reported that intravenous allogeneic mesenchymal stem cells [i.e., mesenchymal stromal cells (MSCs)] improved the neurological behaviors of patients with chronic stroke and substantial functional deficits. Zhang et al [15] showed that the intracerebral injection of neural stem cells improved the neurological functions of patients with paralysis after an ischemic stroke. Guo et al [16] reported that transplanting olfactory ensheathing cells in a patient with cerebral infarction sequela could improve his quality of life.…”