Cell therapy represents a fundamentally different approach to treating neurodegenerative diseases by transplanting living cells into the brain to replace lost [neurons](/entities/neurons), provide trophic support, or modulate the immune system. While still largely experimental, this modality offers the unique potential to regenerate damaged neural circuits—a goal no other therapeutic approach can achieve["@barker2023"]. The field has evolved from early experiments with fetal tissue transplantation to sophisticated approaches using induced pluripotent stem cells (iPSCs) and engineered cell populations.
Mechanism of Action
Cell therapies work through several mechanisms:
Neuronal Replacement
Transplanting neurons or neuronal progenitors to replace lost cells
Establishing synaptic connections with host neurons
Restoring neural circuit function
Glial Cell Replacement
Providing healthy [microglia](/cell-types/microglia-neuroinflammation) to replace dysfunctional cells
Supporting neuronal survival and function
Modulating the brain immune environment
Trophic Factor Delivery
Cells engineered to secrete neurotrophic factors
Supporting survival of endogenous neurons
Promoting plasticity and repair
Immunomodulation
Regulatory immune cells to dampen neuroinflammation
Modulating the brain's immune response
Reducing toxic inflammation
Clinical Programs
Stem Cell Approaches
Key Development Programs
Parkinson's Disease
iPSC-derived dopaminergic neurons: Clinical trials underway in Japan using patient-derived iPSCs[@takahashi2023]
Allogeneic hESC-derived neurons: BlueRock Therapeutics and others in early trials
Mesenchymal stem cells: Immunomodulatory and trophic effects
Amyotrophic Lateral Sclerosis
Neural progenitor cells: Phase 2 trial showed possible slowed progression[@glass2016]
MSC-NTF cells: Phase 1/2 showing safety and potential efficacy
iPSC-derived motor neurons: Preclinical
Alzheimer's Disease
Cholinergic neurons: Early development
Glial progenitor cells: Myelin repair and neuroprotection
Microglial replacement: Aspen Neuroscience program
Encapsulated Cell Biodelivery
An alternative approach involves encapsulating cells that secrete therapeutic proteins:
[Barker, R. A., et al., (2023). Human pluripotent stem cell-derived neurons for disease modeling and drug discovery (2023)](https://doi.org/10.1038/s41583-023-00736-1)
[Unknown, Takahashi, J. (2023). iPS cell-based therapy for Parkinson's disease: A clinical trial update (2023)](https://doi.org/10.1016/j.stemcr.2022.12.001)
[Glass, J. D., et al., (2016). A phase 1/2 study of neural stem cell transplantation in ALS (2016)](https://doi.org/10.1002/acn3.278)
Related Hypotheses
From the [SciDEX Exchange](/exchange) — scored by multi-agent debate