Abstract
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. Stem Cells Translational Medicine 2017;6:634–646
Highlights
Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder worldwide, is clinically characterized by a progressive degeneration of dopaminergic (DA) neurons in several dopaminergic networks [1, 2]
This study demonstrated that the injection of human mesenchymal stem cells (hMSCs) 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
Considering the effects of the hMSC secretome on motor coordination, we observed that its injection was able to improve the motor performance of the CM-injected animals when compared with the 6-OHDA group (Fig. 3A)
Summary
Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder worldwide, is clinically characterized by a progressive degeneration of dopaminergic (DA) neurons in several dopaminergic networks [1, 2]. Secretome of MSCs in Parkinson’s Disea6s3e5 treatment, the use of dopamine reuptake inhibitors, DA agonists, and muscarinic antagonists have positive clinical effects [6, 8]. Despite these pharmacological advances, most of these treatments have been shown to be insufficient, presenting some undesirable side effects, long-term inefficiency, and the inability to recover lost DA neurons or to protect the viability of the remaining ones [9,10,11,12,13]. As with drug treatments, the apparent clinical recovery after surgery does not last and the progression of the degenerative process is not avoided [16, 17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
