Table 1.

Take home message

• Grafts of stem cell derived dopamine neurons transplanted

homotopically into the substantia nigra, rather than

ectopically into the striatum offer the possibility

for more complete circuitry repair.

• The close-to-normal efferent and afferent connectivity

of the intranigral grafts points to a remarkable degree of

circuitry reconstruction that far exceeds what has been

possible to achieve with ectopic intrastriatal grafts.

• Despite their ectopic placement the intrastriatal

dopamine neurons grafts receive excitatory and inhibitory

afferents from relevant areas of the host brain allowing

modulation of the graft-induced functional impact on

motor behavior.

• Intranigral grafting is attractive, not only as a

way to achieve more refined functional regulation of the

grafted neurons, but also as a way to obtain more widespread

reinnervation of the dopamine-deficient limbic and

cortical areas.

• Scale up to the 10-fold larger size of the

nigrostriatal system in the human brain is a major

challenge and may require a combined approach where

the growth capacity of the dopamine neurons is increased

by simultaneous administration of growth factors,

such as GDNF.