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TitleImpact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease
Author(s)Teixeira, Fábio Gabriel Rodrigues
Carvalho, Miguel M.
Panchalingam, K. M.
Rodrigues, Ana João
Pinheiro, Bárbara Filipa Mendes
Anjo, Sandra
Manadas, Bruno
Behie, Leo A.
Sousa, Nuno
Salgado, A. J.
KeywordsMesenchymal stem cells
Parkinson ’ s disease
Dopaminergic neurons
Issue date2017
JournalStem Cells Translational Medicine
CitationTeixeira, F. G., Carvalho, M. M., Panchalingam, K. M., Rodrigues, A. J., Mendes‐Pinheiro, B., Anjo, S., ... & Salgado, A. J. (2017). Impact of the secretome of human mesenchymal stem cells on brain structure and animal behavior in a rat model of Parkinson's disease. Stem cells translational medicine, 6(2), 634-646
Abstract(s)Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeutic benefits are mainly due to their secretome, which has been proposed as a possible therapeutic tool for the treatment of Parkinson's disease (PD). Indeed, it has been shown that the MSC secretome increases neurogenesis and cell survival, and has numerous neuroprotective actions under different conditions. Additionally, using dynamic culturing conditions (through computer-controlled bioreactors) can further modulate the MSC secretome, thereby generating a more potent neurotrophic factor cocktail (i.e., conditioned medium). In this study, we have characterized the MSC secretome by proteomic-based analysis, investigating its therapeutic effects on the physiological recovery of a 6-hydroxidopamine (6-OHDA) PD rat model. For this purpose, we injected MSC secretome into the substantia nigra (SNc) and striatum (STR), characterizing the behavioral performance and determining histological parameters for injected animals versus untreated groups. We observed that the secretome potentiated the increase of dopaminergic neurons (i.e., tyrosine hydroxylase-positive cells) and neuronal terminals in the SNc and STR, respectively, thereby supporting the recovery observed in the Parkinsonian rats' motor performance outcomes (assessed by rotarod and staircase tests). Finally, proteomic characterization of the MSC secretome (through combined mass spectrometry analysis and Bioplex assays) revealed the presence of important neuroregulatory molecules, namely cystatin C, glia-derived nexin, galectin-1, pigment epithelium-derived factor, vascular endothelial growth factor, brain-derived neurotrophic factor, interleukin-6, and glial cell line-derived neurotrophic factor. Overall, we concluded that the use of human MSC secretome alone was able to partially revert the motor phenotype and the neuronal structure of 6-OHDA PD animals. This indicates that the human MSC secretome could represent a novel therapeutic for the treatment of PD.
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AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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