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Cell Survival and Clinical Outcome Following Intrastriatal Transplantation in Parkinson Disease

Hagell, Peter, Brundin, Patrik·2001·Journal of Neuropathology & Experimental Neurology
DOI 10.1093/jnen/60.8.741
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Abstract

Intrastriatal transplantation of embryonic dopaminergic neurons is currently explored as a restorative cell therapy for Parkinson disease (PD). Clinical results have varied, probably due to differences in transplantation methodology and patient selection. In this review, we assess clinical trials and autopsy findings in grafted PD patients and suggest that a minimum number of surviving dopaminergic neurons is required for a favorable outcome. Restoration of [18F]-fluorodopa uptake in the putamen to about 50% of the normal mean seems necessary for moderate to marked clinical benefit to occur. Some studies indicate that this may require mesencephalic tissue from 3-5 human embryos implanted into each hemisphere. The volume, density and pattern of fiber outgrowth and reinnervation, as well as functional integration and dopamine release. are postulated as additional important factors for an optimal clinical outcome. For neural transplantation to become a feasible therapeutic alternative in PD, graft survival must be increased and the need for multiple donors of human embryonic tissue substantially decreased or alternate sources of donor tissue developed. Donor cells derived from alternative sources should demonstrate features comparable to those associated with successful implantation of human embryonic tissue before clinical trials are considered.

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Crossref · 10.1093/jnen/60.8.741

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  • The lower dose targets the estimated minimal number of surviving grafted DA neurons required for clinical benefit (100,000).

    “The high dose targets the estimated number of healthy DA neurons in the intact substantia nigra35 (300,000 DA neurons), and the lower dose targets the estimated minimal number of surviving grafted DA neurons required for clinical benefit36 (100,000 DA neurons).”

    From Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease (2025) · cites this paper as [36]

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Metadata

Authors
Hagell, P., & Brundin, P.
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
2001-08
Volume
60
Issue
8
Pages
741-752
ISSN
  • 0022-3069
  • 1554-6578
DOI
10.1093/jnen/60.8.741
Cited by
174
References
0
Language
en

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