title: Neural transplantation in Huntington disease: long-term grafts in two patients.
abstract: OBJECTIVE
  Clinical trials of fetal neural tissue transplantation for Huntington disease (HD) have been conducted with variable clinical results. However, no long-term analysis of graft survival and integration has been published. Here, we report the pathologic findings in two patients with HD who died 74 and 79 months after transplantation.
  
  
  METHODS
  Methods used were pathologic examination, histochemistry, and immunohistochemistry.
  
  
  RESULTS
  Neostriatum from both patients showed typical neuropathologic changes of advanced HD. Surviving grafts were identified in both patients (6/6 sites and 7/8 sites, respectively) as well-demarcated nests within host neostriatum with associated needle tracts. Grafted neurons adopted either dominant calbindin/parvalbumin or calretinin immunoreactivity (IR). Few neurofilament, MAP-2, DARPP-32, tyrosine hydroxylase, or calbindin IR processes traversed the host parenchyma-graft interface despite minimal junctional gliosis. Immunohistochemistry for CD68 showed microgliosis that was more pronounced in host striatum than graft. Scattered CD45 and CD3 IR cells were present within grafts and host parenchyma. No ubiquitin IR neuronal intranuclear inclusions were identified in graft neurons, although these were prevalent in host cells.
  
  
  CONCLUSIONS
  These two autopsies confirm previous findings of neuronal differentiation and survival of transplanted fetal tissue from the ganglionic eminence and also demonstrate viability of neurons from fetal transplants in human neostriatum for more than 6 years. Despite prolonged survival, these grafts had poor integration with host striatum that is likely responsible for lack of clear clinical improvement in these patients.
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Washington Medical Center, Seattle, WA 98104, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Keene
authors.forename: J A
authors.initials: JA
authors.lastname: Sonnen
authors.forename: P D
authors.initials: PD
authors.lastname: Swanson
authors.forename: O
authors.initials: O
authors.lastname: Kopyov
authors.forename: J B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: T D
authors.initials: TD
authors.lastname: Bird
authors.forename: T J
authors.initials: TJ
authors.lastname: Montine
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D016380:Brain Tissue Transplantation / Q000379:methods* / Q000706:statistics & numerical data; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology*; D017809:Fatal Outcome; D005260:Female; D016332:Fetal Tissue Transplantation / Q000379:methods* / Q000706:statistics & numerical data; D005911:Gliosis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D013687:Telencephalon / Q000166:cytology / Q000196:embryology / Q000637:transplantation*; D013995:Time; D017211:Treatment Failure
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins