Cell Therapy in Multiple Sclerosis: Clinical Advances, Limitations, and Future Perspectives from Clinical Studies—A Systematic Review

<b>Background:</b> Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS), characterised by inflammation, demyelination, and progressive neurodegeneration. Although current disease-modifying therapies (DMTs) can reduce relapse rates and inflammatory activity, they rarely stop long-term progression or repair neurological damage. In recent years, cell-based therapies have emerged as promising approaches to promote immune regulation and neuroregeneration in MS. <b>Methods:</b> This review summarises the current clinical evidence from studies in humans investigating cell-based treatments for MS, including autologous haematopoietic stem cell transplantation (AHSCT), mesenchymal stem cells (MSCs), and neural stem or progenitor cells (NSCs). A systematic literature search was performed using PubMed, Scopus, and ClinicalTrials.gov, focusing on human clinical trials that met specific inclusion criteria. <b>Results:</b> Prevailing findings show that AHSCT provides the most consistent benefit, achieving long-term immune reconstitution and remission in patients with highly active relapsing-remitting MS (RRMS), although it carries procedural risks. MSC therapies have demonstrated good safety and biological activity, especially when delivered intrathecally (IT) in progressive MS, though clinical results remain variable. <b>Conclusions:</b> NSC-based treatments are still at an early stage of clinical research but show potential for CNS repair. The main limitations across studies include differences in protocols, small sample sizes, and short follow-up periods. Further large-scale, randomised controlled trials are needed to confirm long-term efficacy, define optimal delivery methods, and establish standardised clinical protocols.