Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

Abstract

The main objective of this phase I trial was to assess the feasibility and safety of microtransplanting human neural stem cell (hNSC) lines into the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Eighteen patients with a definite diagnosis of ALS received microinjections of hNSCs into the gray matter tracts of the lumbar or cervical spinal cord. Patients were monitored before and after transplantation by clinical, psychological, neuroradiological, and neurophysiological assessment. For up to 60 months after surgery, none of the patients manifested severe adverse effects or increased disease progression because of the treatment. Eleven patients died, and two underwent tracheotomy as a result of the natural history of the disease. We detected a transitory decrease in progression of ALS Functional Rating Scale Revised, starting within the first month after surgery and up to 4 months after transplantation. Our results show that transplantation of hNSC is a safe procedure that causes no major deleterious effects over the short or long term. This study is the first example of medical transplantation of a highly standardized cell drug product, which can be reproducibly and stably expanded ex vivo, comprising hNSC that are not immortalized, and are derived from the forebrain of the same two donors throughout this entire study as well as across future trials. Our experimental design provides benefits in terms of enhancing both intra‐ and interstudy reproducibility and homogeneity. Given the potential therapeutic effects of the hNSCs, our observations support undertaking future phase II clinical studies in which increased cell dosages are studied in larger cohorts of patients. stem cells translational medicine 2019;8:887&897

Multi-Functionalized Self-Assembling Peptides as Reproducible 3D Cell Culture Systems Enabling Differentiation and Survival of Various Human Neural Stem Cell Lines

“…other hNSC lines, all derived from fetal brain tissue from distinct fetuses, produced according to GMP standards and candidate for usage in clinical trials for the treatment of neurological disorders (Mazzini et al, 2015(Mazzini et al, , 2019Vescovi, 2017). Biophysical and mechanical support for hNSCs was provided by pureHYDROSAP, a synthetic ECM-like scaffold, entirely made of biomimetic SAPs, with mechanical properties in the range of nervous tissue (100-1000 Pa) (Arani et al, 2015).…”

Defining the adult hippocampal neural stem cell secretome: in vivo versus in vitro transcriptomic differences and their correlation to secreted protein levels

“…Though the disconnect between in vitro and in vivo gene expression may at first suggest that only in vivo studies should be pursued, such a focused approach does not faithfully represent all biologically and therapeutically relevant stem cell sources. Current clinical trials use cultured neural stem cell lines while preclinical models use NSPCs with varying amounts of in vitro processing (Mazzini et al 2019;Ottoboni, Merlini, and Martino 2017;Mendes-Pinheiro et al 2018;Chandanala et al 2014). Thus, analysis of both cultured and acutely isolated stem cells is critical for the development of effective NSPC-based therapies.…”

Imaging Analysis and Evaluation of Neural Stem Cell Intracerebral Migration and Functional Reconstruction Based on Deep Learning

“…It was found that almost all EGFP positive cells were present in SGL (Subgranular Layer), these cells proliferate and migrate to GCL (granule cell layer), expressing growing neuronal markers polysialic acid nerve cell adhesion molecules and microtubule-associated proteins of neuronal precursor cells, and differentiate into mature after 30 days Neurons suggest that cerebral ischemia promotes neurogenesis in the DG area [26]- [28]. In addition, it has been confirmed in the study of the gerbil transient cerebral ischemia model that after 4 weeks of ischemia, the immature neural precursor cells in the hippocampus SGZ (Subgranular Zone) area can be significantly transformed into mature neurons [29]. There are obvious new neurons in the cell layer.…”