Acta Pharmaceutica Sinica B
|
2026, 16(5): 2645-2681
• Reviews •
Cell-based regenerative interventions in Parkinson's disease: Overcoming pharmacological limitations
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Ana Lizeth Padilla1,1,2,2,2,2,2,2,2,2,2, José L. Lanciego3,3,4,4,5,5, Miquel Vila6,4,4,5,5,7,7,2,2, Fernando de Castro8, David Pozo1,4,5, Fernando Rodríguez de Fonseca9,10,1, Antonia Serrano9,3, Javier Sáez-Valero4,4,7,2, Lucía Núñez1,1,2,2,2,2,2,2,2,2,2, Carlos Villalobos2,2,2,2,2,2,2,2,2, Victor Tapias1,1,2,2,2,2,2,2,2,2,2
Affiliations
1 2. Andalusian Network for Clinical and Translational Research in Neurology (NEURO-RECA), Má
2 7. Instituto de Investigació
3 3. Unidad de Gestió
4 4. Centro Andaluz de Biologí
5 5. Department of Medical Biochemistry, Molecular Biology and Immunology, Medical School, University of Seville, Sevilla 41009, Spain;
6 Catalan Institution for Research and Advanced Studies (ICREA), Barcelona 08010, Spain;
7 6. Instituto de Neurociencias de Alicante, Universidad Miguel Herná
8 Instituto Cajal, Consejo Superior de Investigaciones Cientí
9 0. Instituto de Investigació
1 0 1. Unidad Clí
doi: 10.1016/j.apsb.2026.03.031
Outline
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons and the pathological aggregation of α-synuclein. While current pharmacological therapies provide symptomatic relief, they do not halt or reverse disease progression. Cell-based regenerative strategies have emerged as promising approaches to restore DA function and target the complex, multifactorial pathophysiology of PD. This review critically examines current approaches, including transplantation of fetal ventral mesencephalic tissue, pluripotent stem cell-derived midbrain DA progenitors, and in vivo reprogramming of endogenous cells. In addition, supportive cell types, such as mesenchymal stromal cells and carotid body glomus cells, provide neuroprotective and immunomodulatory effects via paracrine signaling. We summarize preclinical and clinical evidence on graft survival, integration, and functional recovery, and discuss key determinants of therapeutic efficacy, including mitochondrial function and bioenergetic integrity, immune compatibility, and biomaterial scaffolding. Despite significant progress, major challenges remain regarding long-term efficacy, graft standardization, and host-graft interactions. Ongoing translational advances are poised to drive the development of disease-modifying cell therapies capable of delivering durable clinical benefits and improving long-term outcomes in PD.
Parkinson's disease
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Dopamine neurons
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Cell-based therapy
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Neuroprotection
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Regeneration
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Stem cells
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Transplantation
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Mitochondrial dysfunction
Ana Lizeth Padilla, José L. Lanciego, Miquel Vila, Fernando de Castro, David Pozo, Fernando Rodríguez de Fonseca, Antonia Serrano, Javier Sáez-Valero, Lucía Núñez, Carlos Villalobos, Victor Tapias.
Cell-based regenerative interventions in Parkinson's disease: Overcoming pharmacological limitations[J].
Acta Pharmaceutica Sinica B,
2026
, 16
(5)
: 2645
-2681
.
DOI: 10.1016/j.apsb.2026.03.031
Year 2026 volume 16 Issue 5
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5
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Article Info
doi: 10.1016/j.apsb.2026.03.031
- Receive Date:2025-08-19
- Online Date:2026-09-17