Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of parkinson’s disease
| Autor: | Daviaud, Nicolas, Garbayo, Elisa, Sindji, Laurence, Martínez-Serrano, Alberto, Schiller, Paul, Montero-Menei, Claudia |
|---|---|
| Přispěvatelé: | Comunidad de Madrid, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL) |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Cell Survival [SDV]Life Sciences [q-bio] Stanniocalcin-1 stomatognathic system Neurotrophin 3 Parkinsonian Disorders Tissue Engineering and Regenerative Medicine parasitic diseases Animals Humans Tissue engineering reproductive and urinary physiology Organotypic slice culture Neural stem cells Drug Carriers Cell Differentiation Cells Immobilized Rats Disease Models Animal nervous system Delayed-Action Preparations embryonic structures Mesenchymal stem cells Laminin Vascular endothelial growth factor Neurotrophin-3 Stem Cell Transplantation |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Stem Cells Translational Medicine Stem Cells Translational Medicine, Wiley, 2015, 4 (7), pp.670-684. ⟨10.5966/sctm.2014-0139⟩ |
| ISSN: | 2010-1716 2157-6564 2157-6580 |
| DOI: | 10.5966/sctm.2014-0139⟩ |
| Popis: | © AlphaMed Press 2015. Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson’s disease (PD). We recently reported the repair and functional recovery after treatment with human marrow-isolated adult multilineage inducible (MIAMI) cells adhered to neurotrophin-3 (NT3) releasing pharmacologically active microcarriers (PAMs) in hemiparkinsonian rats. In order to comprehend this effect, the goal of the present work was to elucidate the survival, differentiation, and neuroprotective mechanisms of MIAMI cells and human neural stem cells (NSCs), both adhering to NT3-releasing PAMs in an ex vivo organotypic model of nigrostriatal degeneration made from brain sagittal slices. It was shown that PAMs led to a marked increase in MIAMI cell survival and neuronal differentiation when releasing NT3. A significant neuroprotective effect of MIAMI cells adhering to PAMs was also demonstrated. NSCs barely had a neuroprotective effect and differentiated mostly into dopaminergic neuronal cells when adhering to PAM-NT3. Moreover, those cells were able to release dopamine in a sufficient amount to induce a return to baseline levels. Reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses identified vascular endothelial growth factor (VEGF) and stanniocalcin-1 as potential mediators of the neuroprotective effect of MIAMI cells and NSCs, respectively. It was also shown that VEGF locally stimulated tissue vascularization, which might improve graft survival, without excluding a direct neuroprotective effect of VEGF on dopaminergic neurons. These results indicate a prospective interest of human NSC/PAM and MIAMI cell/PAM complexes in tissue engineering for PD. Spanish Ministry of Economy and Competitiveness (Grant SAF2010-17167), a grant from the Comunidad de Madrid (Grant S2011-BMD-2336), and Instituto de Salud Carlos III (Redes Tematicas de Investigacion Cooperativa en Salud RD12/0019/0013) to A.M.S. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text