Co-transplantation of autologous Treg cells in a cell therapy for Parkinson’s disease
Open accessAbstract
The specific loss of midbrain dopamine neurons (mDANs) causes major motor dysfunction in Parkinson's disease, which makes cell replacement a promising therapeutic approach 1-4. However, poor survival of grafted mDANs remains an obstacle to successful clinical outcomes 5-8. Here we show that the surgical procedure itself (referred to here as 'needle trauma') triggers a profound host response that is characterized by acute neuroinflammation, robust infiltration of peripheral immune cells and brain cell death. When midbrain dopamine (mDA) cells derived from human induced pluripotent stem (iPS) cells were transplanted into the rodent striatum, less than 10% of implanted tyrosine hydroxylase (TH)+ mDANs survived at two weeks after transplantation. By contrast, TH- grafted cells mostly survived. Notably, transplantation of autologous regulatory T (T reg) cells greatly modified the response to needle trauma, suppressing acute neuroinflammation and immune cell infiltration. Furthermore, intra-striatal co-transplantation of T reg cells and human-iPS-cell-derived mDA cells significantly protected grafted mDANs from needle-trauma-associated death and improved therapeutic outcomes in rodent models of Parkinson's disease with 6-hydroxydopamine lesions. Co-transplantation with T reg cells also suppressed the undesirable proliferation of TH- grafted cells, resulting in more compact grafts with a higher proportion and higher absolute numbers of TH+ neurons. Together, these data emphasize the importance of the initial inflammatory response to surgical injury in the differential survival of cellular components of the graft, and suggest that co-transplanting autologous T reg cells effectively reduces the needle-trauma-induced death of mDANs, providing a potential strategy to achieve better clinical outcomes for cell therapy in Parkinson's disease.
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Cotransplantation of midbrain dopaminergic neurons and autologous regulatory T cells into PD rats improves survival of dopaminergic neurons and motor function.
“cotransplantation of midbrain dopaminergic neurons and autologous regulatory T cells into PD rats improves the survival of dopaminergic neurons and motor function.435”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [435]
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Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
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- Authors
- Park, T.-Y., Jeon, J., Lee, N., Kim, J., Song, B., Kim, J.-H., Lee, S.-K., Liu, D., Cha, Y., Kim, M., Leblanc, P., Herrington, T. M., Carter, B. S., Schweitzer, J. S., & Kim, K.-S.
- Affiliations
- Harvard University (US)
- Yonsei University (KR)
- Corresponding author
- Kim, Kwang-Soo
- ORCID
- Venue
- Nature
- Published
- 2023-07-12
- Volume
- 619
- Issue
- 7970
- Pages
- 606-615
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC12012854
- OpenAlex
- W4384008968
- Cited by
- 128
- References
- 56
- Citations by year
- 2026: 30 · 2025: 44 · 2024: 45 · 2023: 9
- FWCI
- 21.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Massachusetts General Hospital
- McLean Hospital (NS070577)
- National Institutes of Health (R24OD024622, NS070577)
- National Institute of Neurological Disorders and Stroke (R01NS070577, K23NS099380, NS070577, R01NS127391, R01NS129188)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Parkinson's disease, regulatory T cells, co-transplantation, midbrain dopaminergic neurons, iPSC-derived neurons, cell replacement therapy, neuroinflammation, needle trauma, graft survival, immune cell infiltration, striatum, 6-hydroxydopamine lesion, tyrosine hydroxylase
- MeSH terms
- Neuroinflammatory Diseases, Animals, Dopamine, Graft Survival, Humans, Mesencephalon, Parkinson Disease, Time Factors, Tyrosine 3-Monooxygenase, Oxidopamine, Treatment Outcome, Cell Death, Neostriatum, Cell Proliferation, T-Lymphocytes, Regulatory, Mice, Rats, Induced Pluripotent Stem Cells, Dopaminergic Neurons, Cell- and Tissue-Based Therapy
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