[Natural "dopaminotrophic" cell transplant: a new concept in antiparkinsonian therapy].
OBJECTIVE
Parkinson s disease is caused by the degeneration of dopaminergic neurons of substantia nigra projecting to striatum. Cellular substitution represents a potentially treatment once beneficial levodopa effects wear off. A promising therapeutic approach is grafting cells or other vectors which release neuroprotective molecules that stimulate regeneration in the damaged nigrostriatal system or, in other words, that exert a dopaminotrophic action. We have tested the suitability of intrastriatal grafts of extra adrenal chromaffin cells taken from the Zuckerkandl s organ. This paraganglion contains chromaffin cells that express and release glial cell line derived neurotrophic factor (GDNF) and transforming growth factor b1 (TGF b1), both known to protect dopamine cells in vitro and in vivo. Grafts induced a functional recovery of parkinsonian rats which developed over months. The beneficial effects of grafts of the Zuckerkandl s organ were related to long survival of grafted cells, striatal reinnervation, enhancement of dopamine levels in the host striatum, and the cell delivery into the host striatum of GDNF and TGF b1.


CONCLUSIONS
Our result should stimulate research on the clinical applicability of transplants of the Zuckerkandl s organ in Parkinson s disease
Fernández-Espejo
E
E
Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla. Sevilla, España. efespejo@us.es
El Banoua
F
F
Caraballo
I
I
Galán
B
B
Flores
J A
JA
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000601:surgery; D017690:Cell Transplantation; D019439:Chromaffin Cells / Q000166:cytology / Q000637:transplantation*; D004298:Dopamine / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000628:therapy*; D051381:Rats; D012038:Regeneration / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004298:Dopamine