[Natural "dopaminotrophic" cell transplant: a new concept in antiparkinsonian therapy]. / Trasplante de células naturales "dopaminotroficas": nuevo concepto terapéutico antiparkinsoniano.

AIM AND METHOD: 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. CONCLUSION: Our result should stimulate research on the clinical applicability of transplants of the Zuckerkandl s organ in Parkinson s disease

Trasplante de células naturales 'dopaminotróficas': nuevo concepto terapéutico antiparkinsoniano / Natural 'dopaminotrophic' cell transplant: a new concept in antiparkinsonian therapy

Objetivo y desarrollo. La enfermedad de Parkinson se debe a la degeneración de las neuronas dopaminérgicas de la sustancia negra que proyectan a los ganglios basales. La sustitución celular es un tratamiento potencial una vez que los efectos beneficiosos de la levodopa desaparecen. Una terapia prometedora es el trasplante de células u otros vectores, que segreguen moléculas neuroprotectoras capaces de estimular la regeneración del circuito nigroestriatal dañado o, en otras palabras, que ejerzan una acción dopaminotrófica. En mi laboratorio se ha ensayado en ratas parkinsonianas con células cromafines extraadrenales obtenidas del paraganglio de Zuckerkandl.Estas células expresan los factores neurotróficos GDNF y TGFb1, ambos protectores de neuronas dopaminérgicas tanto in vitro como in vivo. Los trasplantes indujeron en las ratas una notable mejoría funcional que evolucionó durante meses. Los efectos funcionales se asociaron a una larga supervivivencia de las células trasplantadas, reinervación estriatal, incremento de los niveles de dopamina en el estriado hospedador y liberación de los factores GDNF y TGFb1 por las células cromafines trasplantadas. Conclusión. Este resultado debería estimular el ensayo de la posible aplicación clínica del trasplante de células cromafines extraadrenales del paraganglio de Zuckerkandl en la enfermedad de Parkinson (AU)

Aim and method. 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. Conclusion. Our result should stimulate research on the clinical applicability of transplants of the Zuckerkandl’s organ in Parkinson’s disease (AU)

Functional regeneration in a rat Parkinson's model after intrastriatal grafts of glial cell line-derived neurotrophic factor and transforming growth factor beta1-expressing extra-adrenal chromaffin cells of the Zuckerkandl's organ.

Intrabrain transplantation of chromaffin cell aggregates of the Zuckerkandl's organ, an extra-adrenal paraganglion that has never been tested for antiparkinsonian treatment, induced gradual improvement of functional deficits in parkinsonian rats. These beneficial effects were related to long survival of grafted cells, striatal reinnervation, and enhancement of dopamine levels in grafted striatum. Grafted cells were not dopaminergics, but they expressed glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-beta(1). These factors were detected in the host striatal tissue, indicating that chromaffin cells secreted them after grafting. Because glial cell line-derived neurotrophic factor possesses neurorestorative properties over dopaminergic neurons, and transforming growth factor-beta(1) is a cofactor that potentiates the neurotrophic actions of GDNF, functional regeneration was likely caused by the chronic trophic action of neurotrophic factors delivered by long-surviving grafted cells. This work should stimulate research on the clinical applicability of transplants of the Zuckerkandl's organ in Parkinson's disease.