REPLY - We recognize the important contributions made by the Swedish groups in Lund and Stockholm to cell therapy for Parkinson's disease and welcome the opportunity to respond to the letter from Drs. Brundin and Björklund. There are several sites where grafting technology can be optimized: precursor cell expansion, neuronal survival and functional integration in vivo.

Our recently published work1 is directed at the first of these issues and makes one specific claim—that functional dopaminergic neurons can be derived from in vitro expanded precursors. There are 30,000 tyrosine hydroxylase-positive (TH+) neurons in the adult rat substantia nigra6. We show that 200,000 precursor-derived TH+ neurons can be obtained per embryo in vitro and that these neurons synthesize and release dopamine in response to depolarization. We also show in vivo that 1,200 TH+ neurons survive from an initial graft of 40,000 TH+ neurons and that these cells lead to functional recovery. Further studies will be needed to compare directly the in vivo survival of dopaminergic neurons derived from expanded precursors with that of primary cell grafts. Historical comparisons are problematic, especially as the studies cited in the above letter3,4 analyzed graft survival 1–6 weeks after transplantation, whereas our study focused on more long-term survival (three months). Although several other studies2,7,8 also claim that TH+ cells can be obtained in culture, our data demonstrate, with in vitro and in vivo measures, that functional dopaminergic neurons can indeed be derived from expanded precursors.

We agree that improving neuronal survival is an important goal and also urge cautious application of new methods in the clinic. To achieve the clinical goals we all seek, it will be useful to have access to precursor populations for the generation of functional neurons.

See “Survival of expanded dopaminergic precursors is critical for clinical trials” by P. Brundin and A. Björklund