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Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03269071\">NCT03269071<\/jats:ext-link>\n                    , EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (\n                    <jats:italic>hf<\/jats:italic>\n                    NPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale \u22656.5, age 18\u201355\u2009years, disease duration 2\u201320\u2009years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to\n                    <jats:italic>hf<\/jats:italic>\n                    NPCs at 2-year follow-up, clearly demonstrating that\n                    <jats:italic>hf<\/jats:italic>\n                    NPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of\n                    <jats:italic>hf<\/jats:italic>\n                    NPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of\n                    <jats:italic>hf<\/jats:italic>\n                    NPCs in a larger cohort of patients.\n                  <\/jats:p>","DOI":"10.1038\/s41591-022-02097-3","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T12:02:57Z","timestamp":1673265777000},"page":"75-85","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":117,"title":["Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 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