Human Striatum Remodelling after Neurotransplantation in Huntington's Disease

Abstract

Background: Restoration of functions in Huntington's disease (HD) by neurotransplantation stems from the formation of a striatum-like structure capable of establishing host connections as a result of grafted striatal neuroblast maturation. For the first time, we demonstrated some developmental steps accomplished by progenitor cells in the brain of an HD patient and analysed the molecular asset of the human primordium. Case Report: Surgery involved bilateral (two sessions) stereotactic, caudate-putaminal transplantation of whole ganglionic eminence fragments from single legally aborted fetuses. MRI showed that the tissue deposits of the left hemisphere grew and joined to constitute a single tissue mass that remodelled basal ganglia anatomy and remained stable in size over time. No evidence of graft growth was observed contralaterally. PET demonstrated increased striatal and stable cortical metabolism. Unified Huntington's Disease Rating Scale assessments demonstrated improvement of motor performances, which faded over the 36-month follow-up. Cognitive performance tended to decrease at a lower rate than before transplantation. Conclusion: The striatal primordium grew into the host brain and this process was associated with metabolic change and some clinical benefit. The study suggests the plasticity and reparative potential of un-manipulated primordium in an era where promising cell-based therapies are still in their infancy.

Direct Comparison of Rat- and Human-Derived Ganglionic Eminence Tissue Grafts on Motor Function

“…Despite this, the safety and efficacy of transplanting hWGE tissue has been investigated in early phase clinical trials, in which HD patients received either cell suspension or diced tissue transplants. The results obtained from follow-up assessments administered up to 6 years postgraft have confirmed the safety of the procedure and the survival of metabolically active tissue transplants (14,15,20,4). Interestingly, in one safety study, three out of five grafted patients demonstrated long-term stabilization of performance on motor and cognitive tasks relative to a nongrafted cohort of patients who demonstrated a progressive deterioration of these functions.…”

Neuroprotective effects of quercetin 4’- O -β- d -diglucoside on human striatal precursor cells in nutrient deprivation condition

“…Briefly, striatal tissue from 9 to 12 weeks old legally aborted human fetuses were obtained according to Italian National Institute of Health ethical guidelines. The use of human fetal tissue for research purposes was approved by the National Ethics Committee and the Committee for investigation in Humans of the University of Florence (Protocol n°678304) (Gallina et al, 2008(Gallina et al, , 2010(Gallina et al, , 2014. Striatal tissue was dissected from 3 human fetuses under sterile conditions, cut into fragments and enzymatically digested by 1 mg/ml collagenase type IV (Sigma-Aldrich Corp., St. Louis, MO, USA) incubation.…”

Is there a place for human fetal-derived stem cells for cell replacement therapy in Huntington's disease?

“…Preliminary evidence of functional efficacy in human transplants comes from a seminal French study that reported human fetal-derived graft survival and significant improvements in both motor and cognitive function in three patients over an approximately six-year period ( Bachoud-Lévi et al., 2000 , Bachoud-Lévi et al., 2006 ). Enhanced FDG-positron emission tomography signal in the frontal cortex of these individuals suggested that the implanted cells had integrated into the striatal neural circuitry and made functional connections with relevant cortical regions ( Gallina et al., 2014 ). The proof-of-concept provided by this study is encouraging and demonstrates that transplantation of “native” developing MSNs into the damaged striatum can produce functional improvements in at least some patients with HD.…”