Journal of Neurology

, Volume 242, Supplement 1, pp S54–S56 | Cite as

Clinical application of neuronal grafts in Parkinson's disease

  • Olle Lindvall


Fetal neural grafts, rich in dopamine neurons, taken from the ventral mesencephalon and implanted into the dopamine-denervated striatum, can reinnervate the striatum, form synaptic contacts with host neurons, release dopamine and improve motor function. In animal models of Parkinson's disease, the improvement resulting from transplantation is dependent on the number of surviving grafted dopamine neurons and the density and extent of graft-derived reinnervation. The major unresolved scientific question at present is not whether neural grafting is better than established drug treatments but if survival and function of such grafts are at all possible in patients with Parkinson's disease. A more general problem is that if cell transplantation is to become clinically useful for a large number of Parkinsonian patients and also be applied in other neurological disorders, alternative sources of donor tissue must be found; several have been proposed, including adrenal medulla cells and sympathetic ganglia but perhaps the most exciting strategy is to implant cells that have been genetically engineered to synthesize and release L-dopa or dopamine.


Dopamine Release Dopamine Adrenal Medulla Dopamine Neuron Synaptic Contact 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Brundin P, Strecker RE, Widner H, Clarke DJ, Nilsson OG, Astedt B, Lindvall O and Bjorklund A (1988) Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release. Exp Brain Res 70: 192–208Google Scholar
  2. 2.
    Dunnett SB (1991) Transplantation of embryonic dopamine neurons; what we know from rats. J Neurol 238: 65–74Google Scholar
  3. 3.
    Dunnett SB and Annett LE (1991) Nigral transplants in primate models of parkinsonism. In: Eds. O. Lindvall, A. Bjorklund and H Widner. Intracerebral Transplantation in Movement Disorders. Experimental Basis and Clinical Experiences. Amsterdam: Elsevier Science Publishers pp 27–51Google Scholar
  4. 4.
    Fisher LJ, Jinnah HA, Kale LC, Higgins GA, Gage FH (1991) Survival and function of intrastriatally grafted primary fibroblasts genetically modified to produce L-dopa. Neuron 5: 371–380Google Scholar
  5. 5.
    Horellou P, Brundin P, Kalen P, Mallet J and Bjorklund A (1990) In vivo release of DOPA and dopamine from genetically engineered cells grafted to the denervated rat striatum. Neuron 5: 393–402Google Scholar
  6. 6.
    Hyman C, Hofer M, Barde Y-A, Juhasz M, Yancopoulus GD, Squinto SP and Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350: 230–232Google Scholar
  7. 7.
    Jiao S, Gurevich V and Wolff JA (1993) Long-term correction of rat model of Parkinson's disease by gene therapy. Nature 362: 450–453Google Scholar
  8. 8.
    Lin LF, Doherty DH, Lile JD, Bektesh S and Collins F (1993) GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260: 1130–1132Google Scholar
  9. 9.
    Lindvall O (1994) Neural transplantation in Parkinson's disease. In: Eds. Dunnett SB, Bjorklund A, eds Functional Neural Transplantation. New York: Raven Press (in press)Google Scholar
  10. 10.
    Lindvall O, Sawle G, Widner H, Rothwell JC, Bjorklund A, Brooks D, Brundin P, Frackowiak R, Marsden CD, Odin P and Rehncrona S (1994) Evidence for long term survival and function of dopaminergic grafts in progressive Parkinson's disease. Ann Neurol 35: 172–180Google Scholar
  11. 11.
    Wolff JA, Fisher LJ, Xu L, Jinnah HA, Langlais PJ, Iuvone PM, O'Malley KL, Rosenberg MB, Shimohama S, Friedmann T and Gage FH (1989) Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease. Proc Natl Acad Sci USA 86: 9011–9014Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Olle Lindvall
    • 1
  1. 1.Restorative Neurology Unit, Department of NeurologyUniversity HospitalLundSweden

Personalised recommendations