Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain
Open accessAbstract
Significance: Parkinson’s disease is the most common movement disorder. Here we describe the histopathological analysis of a unique patient with Parkinson’s disease who underwent unilateral cell transplantation in the putamen with human embryonic mesencephalic tissue at 24 y before death. The patient enjoyed major clinical benefits for at least a decade after transplantation. After a quarter of a century, complete graft-derived dopaminergic reinnervation was still evident in the transplanted putamen. α-Synuclein–positive inclusions, some with the appearance of typical Lewy bodies, were present in 11–12% of the grafted dopaminergic neurons, reflecting spread of pathology from the host brain to the transplant. The clinical improvements were gradually lost from 14 y posttransplantation, indicating that even extensive graft-derived dopaminergic reinnervation loses its efficacy in a severely degenerating brain.
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The percentage of grafted dopaminergic neurons with detectable LRP increased to 11-12% after 24 years.
“These studies showed that 1-5% of the grafted dopaminergic neurons exhibited detectable LRP 12-22 years post-transplantation (n=2 patients [205], n=1 patient [206], n=3 patients [207]), which increased to 11-12% after 24 years (n=1 patient [208]).”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [208]
The most widely cited studies in support of the prion-like spread of LRP come from post-mortem studies of two PD patient cohorts who received robust long-term intrastriatal grafts of human fetal midbrain tissue.
“The most widely cited studies in support of the prion-like spread of LRP comes from post-mortem studies of two PD patient cohorts who received robust long-term intrastriatal grafts of human fetal midbrain tissue [205–208].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [208]
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Cites
Estimation of nuclear population from microtome sections
Abercrombie, M. (1946) · The Anatomical Record · doi:10.1002/ar.1090940210 · Cited by 4,363 · see citing works
Li, J.-Y., Englund, E., Holton, J. L., Soulet, D., Hagell, P., Lees, A. J., Lashley, T., Quinn, N. P., Rehncrona, S., Björklund, A., et al. (2008) · Nature Medicine · doi:10.1038/nm1746 · Cited by 1,845 · see citing works
Self-citationLewy body–like pathology in long-term embryonic nigral transplants in Parkinson's disease
Kordower, J. H., Chu, Y., Hauser, R. A., Freeman, T. B., & Olanow, C. W. (2008) · Nature Medicine · doi:10.1038/nm1747 · Cited by 1,722 · see citing works
Core assessment program for intracerebral transplantations (CAPIT)
Langston, J. W., Widner, H., Goetz, C. G., Brooks, D. J., Fahn, S., Freeman, T., & Watts, R. L. (1992) · Movement Disorders · doi:10.1002/mds.870070103 · Cited by 1,007 · see citing works
Self-citationQuantitative Analysis of Histological Staining and Fluorescence Using ImageJ
Jensen, E. C. (2013) · The Anatomical Record · doi:10.1002/ar.22641 · Cited by 946 · see citing works
Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient
Piccini, P. P., Brooks, D. J., Björklund, A., Gunn, R. N., Grasby, P. M., Rimoldi, O. E., Brundin, P., Hagell, P., Rehncrona, S., Widner, H., et al. (1999) · Nature Neuroscience · doi:10.1038/16060 · Cited by 700 · see citing works
Self-citationLindvall, O., Sawle, G. V., Widner, H., et al. (1994) · Annals of Neurology · doi:10.1002/ana.410350208 · Cited by 463 · see citing works
Self-citationGrealish, S., Diguet, E., Kirkeby, A., Mattsson, B., Heuer, A., Bramoullé, Y., Camp, N. V., Perrier, A. L., Hantraye, P., Björklund, A., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.09.017 · Cited by 448 · see citing works
Self-citationDyskinesias following neural transplantation in Parkinson's disease
Hagell, P., Piccini, P. P., Björklund, A., Brundin, P., Rehncrona, S., Widner, H., Crabb, L., Pavese, N., Oertel, W. H., Quinn, N. P., et al. (2002) · Nature Neuroscience · doi:10.1038/nn863 · Cited by 444 · see citing works
Self-citationMendez, I. M., Sánchez‐Pernaute, R., Cooper, O., Viñuela, Á., Ferrari, D., Björklund, L., Dagher, A., & Ole Isacson, A. (2005) · Brain · doi:10.1093/brain/awh510 · Cited by 438 · see citing works
Thored, P., Heldmann, U., Gomes‐Leal, W., Gisler, R., Darsalia, V., Taneera, J., Nygren, J. M., Jacobsen, S. W., Ekdahl, C. T., Kokaia, Z., et al. (2009) · Glia · doi:10.1002/glia.20810 · Cited by 378 · see citing works
Wenning, G. K., Odin, P., Morrish, P., Rehncrona, S., Widner, H., Brundin, P., Rothwell, J. C., Brown, R. G., Gustavii, B., Hagell, P., et al. (1997) · Annals of Neurology · doi:10.1002/ana.410420115 · Cited by 369 · see citing works
Self-citationLindvall, O., Widner, H., Rehncrona, S., Brundin, P., Odin, P., Gustavii, B., Frackowiak, R. S. J., Leenders, K. L., Sawle, G. V., Rothwell, J. C., et al. (1992) · Annals of Neurology · doi:10.1002/ana.410310206 · Cited by 358 · see citing works
Self-citationNeuroanatomy and Pathology of Sporadic Parkinson's Disease
Braak, H., & Tredici, K. D. (2008) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-540-79850-7 · Cited by 297 · see citing works
Factors affecting the clinical outcome after neural transplantation in Parkinson's disease
Piccini, P. P., Pavese, N., Hagell, P., Reimer, J., Björklund, A., Oertel, W. H., Quinn, N. P., Brooks, D. J., & Lindvall, O. (2005) · Brain · doi:10.1093/brain/awh649 · Cited by 254 · see citing works
Self-citationLi, J., Englund, E. M., Widner, H., Rehncrona, S., Björklund, A., Lindvall, O., & Brundin, P. (2010) · Movement Disorders · doi:10.1002/mds.23012 · Cited by 214 · see citing works
Self-citationStereological length estimation using spherical probes
Mouton, P. R., Gokhale, A. M., Ward, N. L., & West, M. J. (2002) · Journal of Microscopy · doi:10.1046/j.1365-2818.2002.01006.x · Cited by 203 · see citing works
Long-Term Health of Dopaminergic Neuron Transplants in Parkinson's Disease Patients
Hallett, P. J., Cooper, O., Sadi, D., Robertson, H. A., Mendez, I. M., & Ole Isacson, A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.05.027 · Cited by 156 · see citing works
Kurowska, Z., Englund, E. M., Widner, H., Lindvall, O., Li, J., & Brundin, P. (2011) · Journal of Parkinson s Disease · doi:10.3233/jpd-2011-11004 · Cited by 120 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model
Kikuchi, T., Morizane, A., Doi, D., Magotani, H., Onoe, H., Hayashi, T., Mizuma, H., Takara, S., Takahashi, R., Inoue, H., et al. (2017) · Nature · doi:10.1038/nature23664 · Cited by 702 · see citing works
α-synuclein in the pathophysiology of Alzheimer’s disease
Twohig, D., & Nielsen, H. M. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0320-x · Cited by 374 · see citing works
Doi, D., Magotani, H., Kikuchi, T., Ikeda, M., Hiramatsu, S., Yoshida, K., Amano, N., Nomura, M., Umekage, M., Morizane, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17165-w · Cited by 350 · see citing works
Like prions: the propagation of aggregated tau and α-synuclein in neurodegeneration
Goedert, M., Masuda-Suzukake, M., & Falcon, B. (2017) · Brain · doi:10.1093/brain/aww230 · Cited by 323 · see citing works
MHC matching improves engraftment of iPSC-derived neurons in non-human primates
Morizane, A., Kikuchi, T., Hayashi, T., Mizuma, H., Takara, S., Doi, H., Mawatari, A., Glasser, M. F., Shiina, T., Ishigaki, H., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00926-5 · Cited by 244 · see citing works
Microglia affect α-synuclein cell-to-cell transfer in a mouse model of Parkinson’s disease
George, S., Rey, N. L., Tyson, T., Esquibel, C., Meyerdirk, L., Schulz, E., Pierce, S., Burmeister, A. R., Madaj, Z., Steiner, J. A., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0335-3 · Cited by 229 · see citing works
Self-citationNew approaches for brain repair-from rescue to reprogramming
Barker, R. A., Götz, M., & Parmar, M. (2018) · Nature · doi:10.1038/s41586-018-0087-1 · Cited by 214 · see citing works
Manfredsson, F. P., Luk, K. C., Benskey, M. J., Gezer, A., Garcia, J., Kuhn, N. C., Sandoval, I. M., Patterson, J. R., O'Mara, A., Yonkers, R., et al. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.01.008 · Cited by 199 · see citing works
Liu, D., Guo, J.-J., Su, J.-H., Svanbergsson, A., Yuan, L., Haikal, C., Li, W., Gouras, G., & Li, J.-Y. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-021-00242-5 · Cited by 32 · see citing works
Self-citationHuntington, T. E., & Srinivasan, R. (2021) · Aging and disease · doi:10.14336/ad.2021.0517 · Cited by 34 · see citing works
- Authors
- Li, W., Englund, E., Widner, H., Mattsson, B., van Westen, D., Lätt, J., Rehncrona, S., Brundin, P., Björklund, A., Lindvall, O., & Li, J.-Y.
- Affiliations
- Lund University (SE)
- Skåne University Hospital (SE)
- Center for Medical Imaging and Physiology, Lund University Hospital, 221 85 Lund, Sweden;
- Van Andel Institute (US)
- Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden;
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-05-02
- Volume
- 113
- Issue
- 23
- Pages
- 6544-6549
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4988567
- OpenAlex
- W2347094772
- Cited by
- 313
- References
- 19
- Citations by year
- 2026: 11 · 2025: 29 · 2024: 28 · 2023: 24 · 2022: 27 · 2021: 34 · 2020: 49 · 2019: 30 · 2018: 32 · 2017: 34 · 2016: 14
- FWCI
- 27.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Swedish Research Council (BAGADILICO Linnaeus consortium)
- Lund University (MiltiPark Strategic Research Area)
- Torsten Soderberg Foundation (Research Grant)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, dopaminergic neuron transplantation, graft survival, putamen, striatal reinnervation, Lewy bodies, alpha-synuclein, ubiquitin-positive inclusions, immune response, postmortem histopathology
- MeSH terms
- Corpus Striatum, Dopamine, Humans, Mesencephalon, Neurons, Parkinson Disease, Putamen, Fetal Tissue Transplantation, alpha-Synuclein
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