The few HD transplanted cases that have undergone autopsy [22,42–

The few HD transplanted cases that have undergone autopsy [22,42–46] offer a unique window into the events that take place around and within grafted tissue when placed in a pathological context. The information derived from each post-mortem analysis is invaluable and critical to the implementation of significant improvements of transplantation strategies. Bachoud-Lévi et al., Lancet 2000 [48]

(1 year) Gaura et al., Brain 2004 [49] (2 years) Bachoud-Lévi et al., Lancet Neurol 2006 [50] (6 years) Krystkowiak et al., PLoS ONE 2007 [51] (n = 13) Rosser et al., J Neurol Neurosurg Psychiatry 2002 [19] (6 months) Barker et al., J Neurol Neurosurg GS-1101 in vivo Psychiatry 2013 [41] (3–10 years) Gallina et al., Exp Neurol 2008 [52] (15 months) Gallina et al., Exp Neurol 2010 [21] (18 to 34 months) 1–2/7–9 weeks 25–43 mm Keene et al., Neurology 2007 [46] (6–7 years) Keene et al., Acta Neuropathol 2009 [45] (10 years) GSK-3 inhibition Freeman et al., Proc Natl Acad Sci USA 2000 [42] (18 months) Cicchetti et al., Proc Natl Acad Sci USA 2009 [43] (9, 9.5 and 10 years) Cisbani et al., Brain 2013 [44] (9 and 12 years) In the last decade, our group has undertaken a series of unique studies on the post-mortem analysis of brains obtained from HD patients who have taken part in a clinical trial initiated by the University of South Florida (Table 1)

[17,42–44]. A few additional cases from American and European cohorts have been investigated post-mortem (Table 2). Capetian et al. have recently described one case from the University of Freiburg trial who died 6 months following the transplant procedure [22]. The group of Keene and collaborators who leads the California trial, have published the post-mortem analyses

of three of their cases who have come to autopsy 6, 7 [46] and 10 years [45] after transplantation. In total, the post-mortem analyses of nine cases originating from three distinct clinical trials have been reported (Tables 2 and 3) [22,42–46]. Despite this limited number of cases, each of them has yielded critical and unique information on how grafted foetal tissue behaves in a severely diseased brain and how this may account for the suboptimal clinical outcomes reached. Notwithstanding until discrepancies in the methodologies used in each of the three trials, these post-mortem studies further lead one to hypothesize about how long-term graft survival may be affected by factors such as tissue dissection, cell preparation methods and patient selection. Finally, this review discusses the possible factors influencing graft survival, with a particular emphasis on the post-mortem data. 8/10 (9 years) 9/11 (9.5 years) 1/16 (10 years) None Cysts and mass lesions 8/10 (9 years) 11/11 (12 years) In all clinical trials of cell transplantation in HD patients, postoperative magnetic resonance imaging (MRI) has been used to confirm graft placement (Table 1).

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