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Tracking human neurologic disease status in mouse brain/plasma using reporter-tagged, EV-associated biomarkers.
Maalouf, Katia E; Vaine, Christine A; Frederick, Dawn M; Yoshinaga, Akiko; Obuchi, Wataru; Mahjoum, Shadi; Nieland, Lisa; Al Ali, Jamal; Bragg, D Cristopher; Breakefield, Xandra O; Breyne, Koen.
Afiliación
  • Maalouf KE; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
  • Vaine CA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
  • Frederick DM; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Yoshinaga A; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Obuchi W; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Mahjoum S; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Nieland L; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Al Ali J; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Bragg DC; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
  • Breakefield XO; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA; Center for Molecular Imaging Research, Department of Radiology, Massachuset
  • Breyne K; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA. Electronic address: kbrey
Mol Ther ; 31(7): 2206-2219, 2023 07 05.
Article en En | MEDLINE | ID: mdl-37198883
X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease caused by a retrotransposon insertion in intron 32 of the TAF1 gene. This insertion causes mis-splicing of intron 32 (TAF1-32i) and reduced TAF1 levels. TAF1-32i transcript is unique to XDP patient cells and can be detected in their extracellular vesicles (EVs). We engrafted patient and control iPSC-derived neural progenitor cells (hNPCs) into the striatum of mice. To track TAF1-32i transcript spread by EVs, we transduced the brain-implanted hNPCs with a lentiviral construct called ENoMi, which consists of a re-engineered tetraspanin scaffold tagged with bioluminescent and fluorescent reporter proteins under an EF-1α promoter. Alongside this improved detection in ENoMi-hNPCs-derived EVs, their surface allows specific immunocapture purification, thereby facilitating TAF1-32i analysis. Using this ENoMi-labeling method, TAF1-32i was demonstrated in EVs released from XDP hNPCs implanted in mouse brains. Post-implantation of ENoMi-XDP hNPCs, TAF1-32i transcript was retrieved in EVs isolated from mouse brain and blood, and levels increased over time in plasma. We compared and combined our EV isolation technique to analyze XDP-derived TAF1-32i with other techniques, including size exclusion chromatography and Exodisc. Overall, our study demonstrates the successful engraftment of XDP patient-derived hNPCs in mice as a tool for monitoring disease markers with EVs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Neurodegenerativas / Vesículas Extracelulares Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Neurodegenerativas / Vesículas Extracelulares Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos