As an additional concern, several groups have reported the spread of alpha-synuclein aggregates and Lewy body pathology from Parkinsonian host to donor cells, thereby recruiting the donor neurons into the disease process (Kordower et al., 2008; Li et al., 2008). That said, the quantitative significance of this observation remains contentious (Mendez et al., 2008), and the persistence of donor cells after over a decade following transplantation suggests biological, if not clinical, durability. Nonetheless, the combination of unknown host-to-donor disease spread, unclear requirements for immunosuppression, and unclear dose optimization, necessarily suggest caution as this cell therapeutic strategy advances to the clinic. In particular, the risks and unknowns of this approach must be weighed against the ready availability of both effective pharmacotherapy for Parkinson’s disease, and of effective strategies for deep brain stimulation to mitigate disease severity. Patients refractory to each of these approaches, and not otherwise cognitively impaired, comprise a distinct minority; whether the benefits of stem cell-derived dopaminergic cell transplant to these patients will prove sufficient to justify its development, costs and risks remains to be established (Buttery and Barker, 2014).
