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Additional file 1. Supplementary materials and methods.

Additional file 2: Figure S1. ALSFRS-R slope for each patient in run-in, and 3-, 6- and 12-month follow up after AstroRx® treatment. Figure S2. Serum levels of Nfl for each patient. Table S1. List of serious TEAEs. Table S2. Treatment emergent adverse events (TEAE) reported in at least 20% of patients in both treatment arms. Table S3. AEs related to IT injection of AstroRx cells by lumbar puncture. Table S4. AEs related to immunosuppression by Mycophenolate Mofetil. Table S5. Slope analysis of handheld dynamometer megascore. Table S6. %SVC slopes analysis in run-in, and 3-, 6- and 12-month follow up after AstroRx® treatment

Astrocytes are the most abundant glial cells in the central nervous system (CNS) and play a pivotal role in CNS homeostasis and functionality. Malfunction of astrocytes was implicated in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), Alzheimer’s disease (AD), and multiple sclerosis (MS). The involvement of astrocytes in the pathology of neurodegenerative disorders supports the rationale of transplantation of healthy human astrocytes that can potentially compensate for diseased endogenous astrocytes. In this review, we will focus on the roles of astrocytes in the healthy CNS and under MS conditions. We will describe the cell sources and current cell-based therapies for MS with a focus on the potential of astrocyte transplantation. In addition, we will cover immerging early-stage clinical trials in MS that are currently being conducted using cell-based therapies.

Figure S2. Effect of hES-AS transplantation on disease onset, progression and survival in hSOD1G93A mice. hES-AS, differentiated for 7 days, transplanted intrathecally through CM of hSOD1G93A mice. A Three experimental groups tested, single injection of 2 × 106 hES-AS on day 67 of life (Cellsx1), two injections of 2 × 106 hES-AS each on days 67 and 97 (Cellsx2) and once sham-injected mice (vehicle). Kaplan–Meir plot of disease onset (measured by 3% body weight loss from maximal weight) showing more delay in twice-injected group. B Kaplan–Meier survival curves with similar trends. C Body weight maintained longer in hES-AS-treated mice. Note that a few days after second injection, day 97, weight loss occurred related to injection. D Neurological score. E Significant improvement in motor performance (Rotarod test) for hSOD1 mice transplanted twice with hES-AS. C, D Values are mean ± SEM (PDF 262 kb)

Table S1. Secretome analysis of hES-AS, differentiated for 7Â days or 28Â days. The 220 most secreted factors by the 7-day differentiated hES-AS sorted by mean ng/ml/106 cells Âą SD (PDF 140 kb)

Figure S1. hES-AS produce and secrete neurotrophic factors. Conditioned media of 24Â h from cultures of hES-AS differentiated for 28Â days as well as cell extracts used to measure level of neurotrophic factors GDNF, BDNF, VEGF and IGF-1. For each factor, bars show cell content, amount secreted and negative control (medium only), expressed in pg/106 cells (triplicates Âą SD) (PDF 91 kb)