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Transposon-mediated glial cell line-derived neurotrophic factor overexpression in human adipose tissue-derived mesenchymal stromal cells: A potential approach for neuroregenerative medicine?
Rasinska, Justyna; Klein, Charlotte; Stahn, Laura; Maidhof, Felix; Pfeffer, Anna; Schreyer, Stefanie; Gossen, Manfred; Kurtz, Andreas; Steiner, Barbara; Hemmati-Sadeghi, Shabnam.
Afiliación
  • Rasinska J; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Klein C; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Stahn L; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Maidhof F; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Pfeffer A; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Schreyer S; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Gossen M; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Virchow Campus, Berlin, Germany.
  • Kurtz A; Institute of Active Polymers, Helmholtz-Zentrum Geesthacht, Teltow, Germany.
  • Steiner B; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Virchow Campus, Berlin, Germany.
  • Hemmati-Sadeghi S; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
J Tissue Eng Regen Med ; 16(6): 515-529, 2022 06.
Article en En | MEDLINE | ID: mdl-35278347
Glial cell line-derived neurotrophic factor (GDNF) has neuroprotective effects and may be a promising candidate for regenerative strategies focusing on neurodegenerative diseases. As GDNF cannot cross the blood-brain barrier to potentially regenerate damaged brain areas, continuous in situ delivery with host cells is desired. Here, a non-viral Sleeping Beauty transposon was used to achieve continuous in vitro overexpression of GDNF in immune-privileged human adipose tissue-derived mesenchymal stromal cells (GDNF-tASCs). In addition, in vivo survival, tolerance, and effectiveness of transfected cells were tested in a very mild 6-hydroxydopamine (6-OHDA)-induced dopamine depletion rat model by means of intrastriatal injection on a sample basis up to 6 months after treatment. GDNF-tASCs showed vast in vitro gene overexpression up to 13 weeks post-transfection. In vivo, GDNF was detectable 4 days following transplantation, but no longer after 1 month, although adipose tissue-derived mesenchymal stromal cells (ASCs) could be visualized histologically even after 6 months. Despite successful long-term in vitro GDNF overexpression and its in vivo detection shortly after cell transplantation, the 6-OHDA model was too mild to enable sufficient evaluation of in vivo disease improvement. Still, in vivo immunocompatibility could be further examined. ASCs initially induced a pronounced microglial accumulation at transplantation site, particularly prominent in GDNF-tASCs. However, 6-OHDA-induced pro-inflammatory immune response was attenuated by ASCs, although delayed in the GDNF-tASCs group. To further test the therapeutic potential of the generated GDNF-overexpressing cells in a disease-related context, a follow-up study using a more appropriate 6-OHDA model is needed.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor Neurotrófico Derivado de la Línea Celular Glial / Células Madre Mesenquimatosas Tipo de estudio: Observational_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Tissue Eng Regen Med Asunto de la revista: BIOTECNOLOGIA / HISTOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor Neurotrófico Derivado de la Línea Celular Glial / Células Madre Mesenquimatosas Tipo de estudio: Observational_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Tissue Eng Regen Med Asunto de la revista: BIOTECNOLOGIA / HISTOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido