title: Striatal allografts in patients with Huntington's disease: impact of diminished astrocytes and vascularization on graft viability.
abstract: Neuronal transplantation has been proposed as a potential therapy to replace lost neurons in Huntington's disease. Transplant vascularization and trophic support are important for graft survival. However, very few studies have specifically addressed graft vascularization in patients with neurological disorders. In the present study, we analysed the vasculature of the host putamen and solid grafts of foetal striatal tissue transplanted into patients with Huntington's disease 9 and 12 years previously. Grafts were characterized by a significantly reduced number of large calibre blood vessels in comparison with the host brain. There were also significantly fewer astrocytes and gap junctions, suggesting a lack of functional blood-brain barrier components within the grafted tissue. Additionally, grafts demonstrated a nearly complete absence of pericytes (compared with the striatum) that are considered important for vascular stabilization and angiogenesis. Finally, the host striatum had a marked increase in atrophic astrocytes in comparison with controls and grafts. The extent to which the lower number of large calibre vessels and astrocytes within the transplants contributed to suboptimal graft survival is unknown. The marked increase in atrophic astrocytes in the host brain surrounding the grafts suggests that reduced host trophic support may also contribute to poor graft survival in Huntington's disease. A better understanding of the way in which these components support allografted tissue is critical to the future development of cell-based therapies for the treatment of Huntington's disease.
authors: Centre de Recherche du CHUQ, Axe Neurosciences, Boulevard Laurier, Québec, QC G1V 4G2, Canada.
authors: Giulia
authors: G
authors: Cisbani
authors: Thomas B
authors: TB
authors: Freeman
authors: Denis
authors: D
authors: Soulet
authors: Martine
authors: M
authors: Saint-Pierre
authors: Dave
authors: D
authors: Gagnon
authors: Martin
authors: M
authors: Parent
authors: Robert A
authors: RA
authors: Hauser
authors: Roger A
authors: RA
authors: Barker
authors: Francesca
authors: F
authors: Cicchetti
mesh_terms: D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000473:pathology*; D016380:Brain Tissue Transplantation / Q000379:methods / Q000502:physiology*; D002648:Child; D015331:Cohort Studies; D003342:Corpus Striatum / Q000098:blood supply* / Q000196:embryology / Q000637:transplantation; D005260:Female; D016332:Fetal Tissue Transplantation / Q000379:methods / Q000502:physiology*; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D006816:Huntington Disease / Q000473:pathology / Q000601:surgery*; D008297:Male; D010865:Pilot Projects; D011699:Putamen / Q000098:blood supply*; D014184:Transplantation, Homologous / Q000379:methods / Q000502:physiology