In HD, halting immunosuppression did not Pexidartinib manufacturer correlate with graft rejection [160] at early or later time points, except in one case [51]. As we mentioned in previous sections, the post-mortem analyses of HD transplanted cases a decade following grafting revealed a strong immune response cuffing the grafts [43], in conditions where the immunosuppression began 2 weeks before the surgery and continued for 6 months [17]. It is possible that solid tissue grafts, following the withdrawal of the immunosuppressive therapy, may present enhanced antigenic stimulation triggering a more robust inflammatory reaction, as compared with cell suspension grafts [155,156,161–163].

Solid grafts may trigger a stronger immune response also because they still contain the donor vasculature which is highly immunogenic [139]. Finally, the MI-503 in vitro use of multiple donors may represent another important

variable in introducing a number of mismatched HLA tissues [160]. Some of the critical steps to insure the success of the transplant surgery involve the choice of suitable candidates, and the identification of the exact patient characteristics that can predict treatment outcome. Drawing conclusions from the very limited number of studies currently available is obviously a difficult task. Patients recruited so far show important variability regarding their age at the time of transplantation, their symptom duration, their number of CAG repeats, the time of transplantation from diagnosis and their UHDRS motor score. Nevertheless, we have attempted to analyse these parameters to determine whether any factor might account for

the various behaviours observed for transplants between studies. For this purpose, we have excluded the cases analysed at early time points after transplantation [43–46]. We thus arbitrarily assessed graft survival giving a score from 0 (no graft survival) to 5 (all grafts having survived) and performed Spearman correlation analysis with the selected parameters. These analyses, although performed on PD184352 (CI-1040) a very limited number of cases (n = 7), suggested that grafts survived better when implanted in younger patients (Figure 2A; Spearman r = −0.97101, P = 0.0012) who manifested symptoms for a shorter period of time (Figure 2B; Spearman r = −0.9255, P = 0.008). Surprisingly, patients with the higher number of CAG repeats showed better graft survival (Figure 2C; Spearman r = 0.93796, P = 0.0057). Although it is difficult to explain how higher CAG repeats may not be detrimental to graft survival, our analysis suggests that younger patients at earlier phases of disease progression may be better candidates for transplantation, as severe brain atrophy may represent a less than favourable niche for graft survival and integration. Cell therapy offers the possibility to replace degenerated neurones and thereby to improve symptoms and signs in neurodegenerative diseases such as HD.