Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (10): 4623-4632.doi: 10.4103/NRR.NRR-D-25-00816

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Cell-based immunotherapy for neurodegenerative disease: current approaches and bright future

Tomas J. Huerta1, 2, 3, Valentina Urbina-Muñoz1, 2, Valentina Urra-Alvarez1, 2, 4, Cristopher Villablanca1, 2, Luis S. Gomez-Perez1, 2, 5, Barbara Saavedra1, 2, Tomás Contreras1, 2, 4, René L. Vidal1, 2, 3, 4, *   

  1. 1Center for Integrative Biology, Universidad Mayor, Santiago, Chile; 
    2Center for Geroscience, Brain Health and Metabolism, Santiago, Chile; 
    3Escuela Tecnología Médica, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago, Chile; 
    4Escuela de Biotecnología, Universidad Mayor, Santiago, Chile; 
    5Escuela Nutrición y Dietética, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago, Chile
  • Online:2026-10-15 Published:2026-06-11
  • Contact: René L. Vidal, PhD, rene.vidal@umayor.cl.
  • Supported by:
    This work was supported by Fondecyt, No. 1230980 (to RLV), FONDAP Program, No. 15150012 (to RLV), the Doctoral ANID Fellowship, No. 21240735 (to TJH), No. 21240868 (to VUM) and the Postdoctoral ANID Fellowship, No. 3240049 (to LSGP)

Abstract: Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease are characterized by progressive neuronal loss and chronic neuroinflammation, with current treatments remaining largely symptomatic. This review explores the potential of cell-based immunotherapy as a disease-modifying strategy. Advances in stem cell biology and immune engineering have facilitated the development of therapies using mesenchymal stem cells, chimeric antigen receptor T cells, macrophages, regulatory T cells, modified macrophages, and monoclonal antibodies. These approaches aim to regulate immune mechanisms implicated in neurodegeneration, such as microglial activation, systemic inflammation, and immune checkpoint dysregulation. Notably, macrophage-mediated delivery systems, such as genetically modified cells expressing neurotrophic factors or antioxidant enzymes, have demonstrated neuroprotective effects. Likewise, emerging data support T-cell modulation and monoclonal antibody development as therapeutic targets in amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. We highlight current preclinical findings, underlying mechanisms, and translational challenges, emphasizing that immunomodulatory cell therapies represent a promising avenue for precision medicine in neurodegenerative diseases.

Key words: Alzheimer’s disease, amytrophic lateral sclerosis, cell therapy, Huntington’s disease, immunomodulator, immunotherapy, neurodegenerative diseases, Parkinson’s disease