Sandra Anjo - Academia.edu (original) (raw)
Papers by Sandra Anjo
Stem cells translational medicine, 2016
Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeut... more 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 6hydroxidopamine (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. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1-13 SIGNIFICANCE It has been suggested that the therapeutic effects of human mesenchymal stem cells (hMSCs) in central nervous system (CNS) regenerative medicine are mediated by the active secretion of bioactive molecules, which is known as the secretome. This study demonstrated that the injection of hMSC secretome in a 6-hydroxidopamine Parkinson's disease (PD) rat model was able to revert the Parkinsonian phenotype, potentiating the recovery of dopaminergic neurons in both the substantia nigra and striatum, thereby supporting the motor recovery observed in the PD rats. This work shows the modulatory role of the hMSC secretome in brain repair, further indicating that such cell-free therapies could represent the basis of future strategies for the treatment of PD.
Frontiers in Plant Science, 2021
The pinewood nematode (PWN), Bursaphelenchus xylophilus, the pine wilt disease’s (PWD) causal age... more The pinewood nematode (PWN), Bursaphelenchus xylophilus, the pine wilt disease’s (PWD) causal agent, is a migratory endoparasitic nematode skilled to feed on pine tissues and on fungi that colonize the trees. In order to study B. xylophilus secretomes under the stimulus of pine species with different susceptibilities to disease, nematodes were exposed to aqueous pine extracts from Pinus pinaster (high-susceptible host) and P. pinea (low-susceptible host). Sequential windowed acquisition of all theoretical mass spectra (SWATH-MS) was used to determine relative changes in protein amounts between B. xylophilus secretions, and a total of 776 secreted proteins were quantified in both secretomes. From these, 22 proteins were found increased in the B. xylophilus secretome under the P. pinaster stimulus and 501 proteins increased under the P. pinea stimulus. Functional analyses of the 22 proteins found increased in the P. pinaster stimulus showed that proteins with peptidase, hydrolase, and...
Pain
ABSTRACT It remains unknown why upon similar acute/subacute painful conditions, pain persists in ... more ABSTRACT It remains unknown why upon similar acute/subacute painful conditions, pain persists in some individuals while in others it resolves. Genetic factors, mood, and functional alterations, particularly involving the mesolimbic network, appear to be key. In order to explore potential susceptibility/resistance factors, we screened a large population of rats with a peripheral neuropathy and we isolated a small subset (<15%) that presented high thresholds (HT) to mechanical allodynia (reduced pain manifestation). The phenotype was sustained over 12 weeks and was associated with higher hedonic behavior when compared with low threshold subjects (LT). The nucleus accumbens (NAc) of HT and LT animals were isolated for proteomic analysis by Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS). Two hundred and seventy-nine proteins displayed different expression between LT and HT animals/subjects. Among several protein families, the proteasome pathway repeatedly emerged in gene ontology enrichment and KEGG analyses. Several alpha and beta 20S proteasome subunits were increased in LT when compared to HT animals (e.g., PSMα1, PSMα2, and PSMβ5). On the contrary, UBA6, an upstream ubiquitin-activating enzyme, was decreased in LT animals. Altogether these observations are consistent with an overactivation of the accumbal proteasome pathway in animals that manifest pain and depressive-like behaviors after a neuropathic injury. All the proteomic data are available via ProteomeXchange with identifier PXD022478.
Cancer Genomics - Proteomics
Frontiers in Cell and Developmental Biology
International Journal of Molecular Sciences
The well-known antimicrobial effects of chitosan (CS) polymers make them a promising adjuvant in ... more The well-known antimicrobial effects of chitosan (CS) polymers make them a promising adjuvant in enhancing antibiotic effectiveness against human pathogens. However, molecular CS antimicrobial mechanisms remain unclear, despite the insights presented in the literature. Thus, the aim of the present study was to depict the molecular effects implicated in the interaction of low or medium molecular mass CS polymers and their nanoparticle-counterparts against Escherichia coli. The differential E. coli proteomes sensitized to either CS polymers or nanoparticles were investigated by nano liquid chromatography–mass spectrometry (micro-LC-MS/MS). A total of 127 proteins differentially expressed in CS-sensitized bacteria were predominantly involved in (i) structural functions associated to the stability of outer membrane, (ii) increment of protein biosynthesis due to high abundance of ribosomal proteins and (iii) activation of biosynthesis of amino acid and purine metabolism pathways. Antibac...
Translational Neurodegeneration
Background: The identification of circulating biomarkers that closely correlate with Parkinson's ... more Background: The identification of circulating biomarkers that closely correlate with Parkinson's Disease (PD) has failed several times in the past. Nevertheless, in this pilot study, a translational approach was conducted, allowing the evaluation of the plasma levels of two mitochondrial-related proteins, whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls. Methods: The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions, followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states. This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients. Results: From the secretome analysis, several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes. Similarly, two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls. Moreover, a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins. Both proteins are associated with apoptotic mitochondrial changes, which may correspond to potential indicators of cell death. Moreover, one of these proteins, the VPS35 protein, was reported in plasma for the first time, and its quantification was only possible due to its previous identification in the secretome analysis.
Frontiers in Bioengineering and Biotechnology
Parkinson's disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the hum... more Parkinson's disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the human midbrain causing motor dysfunctions. The exact mechanism behind dopaminergic cell death is still not completely understood and, so far, no cure or neuroprotective treatment for PD is available. Recent studies have brought attention to the variety of bioactive molecules produced by mesenchymal stem cells (MSCs), generally referred to as the secretome. Herein, we evaluated whether human MSCs-bone marrow derived (hBMSCs) secretome would be beneficial in a PD pre-clinical model, when compared directly with cell transplantation of hBMSCs alone. We used a 6-hydroxydpomanie (6-OHDA) rat PD model, and motor behavior was evaluated at different time points after treatments (1, 4, and 7 weeks). The impact of the treatments in the recovery of DA neurons was estimated by determining TH-positive neuronal densities in the substantia nigra and fibers in the striatum, respectively, at the end of the behavioral characterization. Furthermore, we determined the effect of the hBMSCs secretome on the neuronal survival of human neural progenitors in vitro, and characterized the secretome through proteomic-based approaches. This work demonstrates that the injection of hBMSCs secretome led to the rescue of DA neurons, when compared to transplantation of hBMSCs themselves, which can explain the recovery of secretome-injected animals' behavioral performance in the staircase test. Moreover, we observed that hBMSCs secretome induces higher levels of in vitro neuronal differentiation. Finally, the proteomic analysis revealed that hBMSCs secrete important exosome-related molecules, such as those related with the ubiquitin-proteasome and histone systems. Overall, this work provided important insights on the potential use of hBMSCs secretome as a therapeutic tool for PD, and further confirms the importance of the secreted molecules rather than the transplantation of hBMSCs for the observed positive effects. These could be likely through normalization of defective processes in PD, namely proteostasis or altered gene transcription, which lately can lead to neuroprotective effects.
Frontiers in Cellular Neuroscience
Frontiers in Cellular Neuroscience
Cellular and Molecular Life Sciences
ABSTRACTThe label-free quantitative mass spectrometry methods, in particular, the SWATH-MS approa... more ABSTRACTThe label-free quantitative mass spectrometry methods, in particular, the SWATH-MS approach, have gained popularity and became a powerful technique for comparison of large datasets. In the present work, it is introduced the use of recombinant proteins as internal standards for untargeted label-free methods. The proposed internal standard strategy reveals a similar intragroup normalization capacity when compared with the most common normalization methods, with the additional advantage of maintaining the overall proteome changes between groups (which are lost using other methods). Therefore, the proposed strategy is able to maintain a good performance even when large qualitative and quantitative differences in sample composition are observed, such as the ones induced by biological regulation (as observed in secretome and other biofluids’ analyses) or by enrichment approaches (such as immunopurifications). Moreover, this approach corresponds to a cost-effective alternative, eas...
Advances in Clinical Chemistry
Veterinary Immunology and Immunopathology
Journal of Proteomics
Dogs develop only some of the components of the human metabolic syndrome (MetS). Thus, in order t... more Dogs develop only some of the components of the human metabolic syndrome (MetS). Thus, in order to study possible MetS-related alterations in dogs, human MetS criteria were adapted to define canine MetS or so-called obesity-related metabolic dysfunction (ORMD). The main objective of this study was to identify changes in the salivary proteome of obese dogs with ORMD in comparison with obese dogs without ORMD which may constitute potential salivary biomarkers for assessing ORMD. In a first phase, 12 adult obese dogs with ORMD (N = 6) and without ORMD (N = 6) were included in the study. Subsequently, and with the aim of validating and strengthening the results, additional 12 obese dogs (6 with and 6 without ORMD) were tested in an independent experiment following the same protocol. Saliva samples were subjected to a quantitative proteomics analysis and the levels of nine salivary proteins were found to be significantly different between groups, among them those which had greatest fold-change were proteins involved in glycolysis and oxidative stress. In conclusion, despite metabolic syndrome to include different combinations of diseases, the observation of differences in salivary proteome suggests a potential of this fluid to understand the pathophysiology of the disease. Significance: This is the first study evaluating proteomes of saliva in dogs, as a non invasive sample, in order to increase knowledge about the metabolic/physiopathological changes related to obesity-related metabolic dysfunction (ORMD) together with the identification of potential biomarkers for its diagnosis. As approximately 20% of dogs with naturally occurring obesity were described to suffer ORMD associated with insulin resistance and hypoadiponectinemia, the fact that indicate possible links between ORMD and associated diseases.
Stem cells translational medicine, Jan 20, 2018
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results fr... more Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results from the death of dopamine (DA) neurons. Over recent years, differentiated or undifferentiated neural stem cells (NSCs) transplantation has been widely used as a means of cell replacement therapy. However, compelling evidence has brought attention to the array of bioactive molecules produced by stem cells, defined as secretome. As described in the literature, other cell populations have a high-neurotrophic activity, but little is known about NSCs. Moreover, the exploration of the stem cell secretome is only in its initial stages, particularly as applied to neurodegenerative diseases. Thus, we have characterized the secretome of human neural progenitor cells (hNPCs) through proteomic analysis and investigated its effects in a 6-hydroxidopamine (6-OHDA) rat model of PD in comparison with undifferentiated hNPCs transplantation. Results revealed that the injection of hNPCs secretome potentiate...
Stem cells translational medicine, 2016
Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeut... more 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 6hydroxidopamine (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. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1-13 SIGNIFICANCE It has been suggested that the therapeutic effects of human mesenchymal stem cells (hMSCs) in central nervous system (CNS) regenerative medicine are mediated by the active secretion of bioactive molecules, which is known as the secretome. This study demonstrated that the injection of hMSC secretome in a 6-hydroxidopamine Parkinson's disease (PD) rat model was able to revert the Parkinsonian phenotype, potentiating the recovery of dopaminergic neurons in both the substantia nigra and striatum, thereby supporting the motor recovery observed in the PD rats. This work shows the modulatory role of the hMSC secretome in brain repair, further indicating that such cell-free therapies could represent the basis of future strategies for the treatment of PD.
Frontiers in Plant Science, 2021
The pinewood nematode (PWN), Bursaphelenchus xylophilus, the pine wilt disease’s (PWD) causal age... more The pinewood nematode (PWN), Bursaphelenchus xylophilus, the pine wilt disease’s (PWD) causal agent, is a migratory endoparasitic nematode skilled to feed on pine tissues and on fungi that colonize the trees. In order to study B. xylophilus secretomes under the stimulus of pine species with different susceptibilities to disease, nematodes were exposed to aqueous pine extracts from Pinus pinaster (high-susceptible host) and P. pinea (low-susceptible host). Sequential windowed acquisition of all theoretical mass spectra (SWATH-MS) was used to determine relative changes in protein amounts between B. xylophilus secretions, and a total of 776 secreted proteins were quantified in both secretomes. From these, 22 proteins were found increased in the B. xylophilus secretome under the P. pinaster stimulus and 501 proteins increased under the P. pinea stimulus. Functional analyses of the 22 proteins found increased in the P. pinaster stimulus showed that proteins with peptidase, hydrolase, and...
Pain
ABSTRACT It remains unknown why upon similar acute/subacute painful conditions, pain persists in ... more ABSTRACT It remains unknown why upon similar acute/subacute painful conditions, pain persists in some individuals while in others it resolves. Genetic factors, mood, and functional alterations, particularly involving the mesolimbic network, appear to be key. In order to explore potential susceptibility/resistance factors, we screened a large population of rats with a peripheral neuropathy and we isolated a small subset (<15%) that presented high thresholds (HT) to mechanical allodynia (reduced pain manifestation). The phenotype was sustained over 12 weeks and was associated with higher hedonic behavior when compared with low threshold subjects (LT). The nucleus accumbens (NAc) of HT and LT animals were isolated for proteomic analysis by Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS). Two hundred and seventy-nine proteins displayed different expression between LT and HT animals/subjects. Among several protein families, the proteasome pathway repeatedly emerged in gene ontology enrichment and KEGG analyses. Several alpha and beta 20S proteasome subunits were increased in LT when compared to HT animals (e.g., PSMα1, PSMα2, and PSMβ5). On the contrary, UBA6, an upstream ubiquitin-activating enzyme, was decreased in LT animals. Altogether these observations are consistent with an overactivation of the accumbal proteasome pathway in animals that manifest pain and depressive-like behaviors after a neuropathic injury. All the proteomic data are available via ProteomeXchange with identifier PXD022478.
Cancer Genomics - Proteomics
Frontiers in Cell and Developmental Biology
International Journal of Molecular Sciences
The well-known antimicrobial effects of chitosan (CS) polymers make them a promising adjuvant in ... more The well-known antimicrobial effects of chitosan (CS) polymers make them a promising adjuvant in enhancing antibiotic effectiveness against human pathogens. However, molecular CS antimicrobial mechanisms remain unclear, despite the insights presented in the literature. Thus, the aim of the present study was to depict the molecular effects implicated in the interaction of low or medium molecular mass CS polymers and their nanoparticle-counterparts against Escherichia coli. The differential E. coli proteomes sensitized to either CS polymers or nanoparticles were investigated by nano liquid chromatography–mass spectrometry (micro-LC-MS/MS). A total of 127 proteins differentially expressed in CS-sensitized bacteria were predominantly involved in (i) structural functions associated to the stability of outer membrane, (ii) increment of protein biosynthesis due to high abundance of ribosomal proteins and (iii) activation of biosynthesis of amino acid and purine metabolism pathways. Antibac...
Translational Neurodegeneration
Background: The identification of circulating biomarkers that closely correlate with Parkinson's ... more Background: The identification of circulating biomarkers that closely correlate with Parkinson's Disease (PD) has failed several times in the past. Nevertheless, in this pilot study, a translational approach was conducted, allowing the evaluation of the plasma levels of two mitochondrial-related proteins, whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls. Methods: The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions, followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states. This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients. Results: From the secretome analysis, several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes. Similarly, two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls. Moreover, a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins. Both proteins are associated with apoptotic mitochondrial changes, which may correspond to potential indicators of cell death. Moreover, one of these proteins, the VPS35 protein, was reported in plasma for the first time, and its quantification was only possible due to its previous identification in the secretome analysis.
Frontiers in Bioengineering and Biotechnology
Parkinson's disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the hum... more Parkinson's disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the human midbrain causing motor dysfunctions. The exact mechanism behind dopaminergic cell death is still not completely understood and, so far, no cure or neuroprotective treatment for PD is available. Recent studies have brought attention to the variety of bioactive molecules produced by mesenchymal stem cells (MSCs), generally referred to as the secretome. Herein, we evaluated whether human MSCs-bone marrow derived (hBMSCs) secretome would be beneficial in a PD pre-clinical model, when compared directly with cell transplantation of hBMSCs alone. We used a 6-hydroxydpomanie (6-OHDA) rat PD model, and motor behavior was evaluated at different time points after treatments (1, 4, and 7 weeks). The impact of the treatments in the recovery of DA neurons was estimated by determining TH-positive neuronal densities in the substantia nigra and fibers in the striatum, respectively, at the end of the behavioral characterization. Furthermore, we determined the effect of the hBMSCs secretome on the neuronal survival of human neural progenitors in vitro, and characterized the secretome through proteomic-based approaches. This work demonstrates that the injection of hBMSCs secretome led to the rescue of DA neurons, when compared to transplantation of hBMSCs themselves, which can explain the recovery of secretome-injected animals' behavioral performance in the staircase test. Moreover, we observed that hBMSCs secretome induces higher levels of in vitro neuronal differentiation. Finally, the proteomic analysis revealed that hBMSCs secrete important exosome-related molecules, such as those related with the ubiquitin-proteasome and histone systems. Overall, this work provided important insights on the potential use of hBMSCs secretome as a therapeutic tool for PD, and further confirms the importance of the secreted molecules rather than the transplantation of hBMSCs for the observed positive effects. These could be likely through normalization of defective processes in PD, namely proteostasis or altered gene transcription, which lately can lead to neuroprotective effects.
Frontiers in Cellular Neuroscience
Frontiers in Cellular Neuroscience
Cellular and Molecular Life Sciences
ABSTRACTThe label-free quantitative mass spectrometry methods, in particular, the SWATH-MS approa... more ABSTRACTThe label-free quantitative mass spectrometry methods, in particular, the SWATH-MS approach, have gained popularity and became a powerful technique for comparison of large datasets. In the present work, it is introduced the use of recombinant proteins as internal standards for untargeted label-free methods. The proposed internal standard strategy reveals a similar intragroup normalization capacity when compared with the most common normalization methods, with the additional advantage of maintaining the overall proteome changes between groups (which are lost using other methods). Therefore, the proposed strategy is able to maintain a good performance even when large qualitative and quantitative differences in sample composition are observed, such as the ones induced by biological regulation (as observed in secretome and other biofluids’ analyses) or by enrichment approaches (such as immunopurifications). Moreover, this approach corresponds to a cost-effective alternative, eas...
Advances in Clinical Chemistry
Veterinary Immunology and Immunopathology
Journal of Proteomics
Dogs develop only some of the components of the human metabolic syndrome (MetS). Thus, in order t... more Dogs develop only some of the components of the human metabolic syndrome (MetS). Thus, in order to study possible MetS-related alterations in dogs, human MetS criteria were adapted to define canine MetS or so-called obesity-related metabolic dysfunction (ORMD). The main objective of this study was to identify changes in the salivary proteome of obese dogs with ORMD in comparison with obese dogs without ORMD which may constitute potential salivary biomarkers for assessing ORMD. In a first phase, 12 adult obese dogs with ORMD (N = 6) and without ORMD (N = 6) were included in the study. Subsequently, and with the aim of validating and strengthening the results, additional 12 obese dogs (6 with and 6 without ORMD) were tested in an independent experiment following the same protocol. Saliva samples were subjected to a quantitative proteomics analysis and the levels of nine salivary proteins were found to be significantly different between groups, among them those which had greatest fold-change were proteins involved in glycolysis and oxidative stress. In conclusion, despite metabolic syndrome to include different combinations of diseases, the observation of differences in salivary proteome suggests a potential of this fluid to understand the pathophysiology of the disease. Significance: This is the first study evaluating proteomes of saliva in dogs, as a non invasive sample, in order to increase knowledge about the metabolic/physiopathological changes related to obesity-related metabolic dysfunction (ORMD) together with the identification of potential biomarkers for its diagnosis. As approximately 20% of dogs with naturally occurring obesity were described to suffer ORMD associated with insulin resistance and hypoadiponectinemia, the fact that indicate possible links between ORMD and associated diseases.
Stem cells translational medicine, Jan 20, 2018
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results fr... more Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results from the death of dopamine (DA) neurons. Over recent years, differentiated or undifferentiated neural stem cells (NSCs) transplantation has been widely used as a means of cell replacement therapy. However, compelling evidence has brought attention to the array of bioactive molecules produced by stem cells, defined as secretome. As described in the literature, other cell populations have a high-neurotrophic activity, but little is known about NSCs. Moreover, the exploration of the stem cell secretome is only in its initial stages, particularly as applied to neurodegenerative diseases. Thus, we have characterized the secretome of human neural progenitor cells (hNPCs) through proteomic analysis and investigated its effects in a 6-hydroxidopamine (6-OHDA) rat model of PD in comparison with undifferentiated hNPCs transplantation. Results revealed that the injection of hNPCs secretome potentiate...