title: Neural and mesenchymal stem cells in animal models of Huntington's disease: past experiences and future challenges.
abstract: Huntington's disease (HD) is an inherited disease that causes progressive nerve cell degeneration. It is triggered by a mutation in the HTT gene that strongly influences functional abilities and usually results in movement, cognitive and psychiatric disorders. HD is incurable, although treatments are available to help manage symptoms and to delay the physical, mental and behavioral declines associated with the condition. Stem cells are the essential building blocks of life, and play a crucial role in the genesis and development of all higher organisms. Ablative surgical procedures and fetal tissue cell transplantation, which are still experimental, demonstrate low rates of recovery in HD patients. Due to neuronal cell death caused by accumulation of the mutated huntingtin (mHTT) protein, it is unlikely that such brain damage can be treated solely by drug-based therapies. Stem cell-based therapies are important in order to reconstruct damaged brain areas in HD patients. These therapies have a dual role: stem cell paracrine action, stimulating local cell survival, and brain tissue regeneration through the production of new neurons from the intrinsic and likely from donor stem cells. This review summarizes current knowledge on neural stem/progenitor cell and mesenchymal stem cell transplantation, which has been carried out in several animal models of HD, discussing cell distribution, survival and differentiation after transplantation, as well as functional recovery and anatomic improvements associated with these approaches. We also discuss the usefulness of this information for future preclinical and clinical studies in HD.
authors.affiliation: Laboratório de Genética, Instituto Butantan, 1500 Av. Vital Brasil, São Paulo, 05503-900, Brazil. irina.kerkis@butantan.gov.br.
authors.forename: Irina
authors.initials: I
authors.lastname: Kerkis
authors.affiliation: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 455 Av. Dr. Arnaldao, São Paulo, 01246903, Brazil.
authors.forename: Monica Santoro
authors.initials: MS
authors.lastname: Haddad
authors.affiliation: CellAvita Ltd, 1470 Al. Santos, 9th floor, block 909, São Paulo, SP, 01418-100, Brazil.
authors.forename: Cristiane Wenceslau
authors.initials: CW
authors.lastname: Valverde
authors.affiliation: SoluBest Ltd, Weizmann Science Park, POB 4053 18 Einstein Street, Ness Ziona, 74140, Israel.
authors.forename: Sabina
authors.initials: S
authors.lastname: Glosman
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology; D002454:Cell Differentiation; D002470:Cell Survival; D004195:Disease Models, Animal; D006801:Humans; D006816:Huntington Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods / Q000639:trends; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology; D058953:Neural Stem Cells / Q000637:transplantation*