Cell secretome based approaches in Parkinson’s disease regenerative medicine

References

• Pires AO, Teixeira FG, Mendes-Pinheiro B, et al. Old and new challenges in Parkinson’s disease therapeutics. Prog Neurobiol. 2017;156:69–89.
   PubMed Web of Science ®Google Scholar
• Calabrese V, Santoro A, Monti D, et al. Aging and Parkinson’s disease: inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis. Free Radic Biol Med. 2018;115:80–91.
   PubMed Web of Science ®Google Scholar
• Benazzouz A, Mamad O, Abedi P, et al. Involvement of dopamine loss in extrastriatal basal ganglia nuclei in the pathophysiology of Parkinson’s disease. Front Aging Neurosci. 2014;6:87.
   PubMed Web of Science ®Google Scholar
• Michel PP, Hirsch EC, Hunot S. Understanding dopaminergic cell death pathways in Parkinson disease. Neuron. 2016;90:675–691.
   PubMed Web of Science ®Google Scholar
• LeWitt PA, Fahn S. Levodopa therapy for Parkinson disease: a look backward and forward. Neurology. 2016;86:S3–12.
   PubMed Web of Science ®Google Scholar
• Jimenez-Shahed J. A review of current and novel levodopa formulations for the treatment of Parkinson’s disease. Ther Deliv. 2016;7:179–191.
   PubMed Web of Science ®Google Scholar
• Jankovic J, Aguilar LG. Current approaches to the treatment of Parkinson’s disease. Neuropsychiatr Dis Treat. 2008;4:743–757.
   PubMedGoogle Scholar
• Fabbri M, Rosa MM, Abreu D, et al. Clinical pharmacology review of safinamide for the treatment of Parkinson’s disease. Neurodegener Dis Manag. 2015;5:481–496.
   PubMed Web of Science ®Google Scholar
• Hariz G-M, Limousin P, Hamberg K. DBS means everything – for some time”. Patients’ perspectives on daily life with deep brain stimulation for Parkinson’s disease. J Parkinsons Dis. 2016;6:335–347.
   PubMedGoogle Scholar
• Parmar M, Torper O, Drouin-Ouellet J. Cell-based therapy for Parkinson’s disease: a journey through decades toward the light side of the force. Eur J Neurosci. 2018;55:4763–4776.
   Google Scholar
• Barker RA, Drouin-Ouellet J, Parmar M. Cell-based therapies for Parkinson disease—past insights and future potential. Nat Rev Neurol. 2015;11:492–503.
   PubMed Web of Science ®Google Scholar
• Bjorklund A, Kordower JH. Cell therapy for Parkinson’s disease: what next?: cell therapy for Parkinson’s disease: what next? Mov Disord. 2013;28:110–115.
   PubMed Web of Science ®Google Scholar
• Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17:11–22.
   PubMed Web of Science ®Google Scholar
• Lo Furno D, Mannino G, Giuffrida R. Functional role of mesenchymal stem cells in the treatment of chronic neurodegenerative diseases. J Cell Physiol. 2018;233:3982–3999.
   PubMed Web of Science ®Google Scholar
• Laroni A, de Rosbo NK, Uccelli A. Mesenchymal stem cells for the treatment of neurological diseases: immunoregulation beyond neuroprotection. Immunol Lett. 2015;168:183–190.
   PubMed Web of Science ®Google Scholar
• Isacson O, Kordower JH. Future of cell and gene therapies for Parkinson’s disease. Ann Neurol. 2008;64:S122–S138.
   PubMed Web of Science ®Google Scholar
• Lindvall O. Clinical translation of stem cell transplantation in Parkinson’s disease. J Intern Med. 2016;279:30–40.
   PubMed Web of Science ®Google Scholar
• Meyerrose T, Olson S, Pontow S, et al. Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors. Adv Drug Deliv Rev. 2010;62:1167–1174.
   PubMed Web of Science ®Google Scholar
• Drago D, Cossetti C, Iraci N, et al. The stem cell secretome and its role in brain repair. Biochimie. 2013;95:2271–2285.
   PubMed Web of Science ®Google Scholar
• Salgado AJ, Sousa JC, Costa BM, et al. Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities. Front Cell Neurosci. 2015;9:249.
   PubMed Web of Science ®Google Scholar
• Teixeira FG, Carvalho MM, Sousa N, et al. Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration? Cell Mol Life Sci. 2013;70:3871–3882.
   PubMed Web of Science ®Google Scholar
• Baraniak PR, McDevitt TC. Stem cell paracrine actions and tissue regeneration. Regen Med. 2010;5:121–143.
   PubMed Web of Science ®Google Scholar
• Yasuhara T, Matsukawa N, Hara K, et al. Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson’s disease. J Neurosci. 2006;26:12497–12511.
   PubMed Web of Science ®Google Scholar
• Mendes-Pinheiro B, Teixeira FG, Anjo SI, et al.. Secretome of undifferentiated neural progenitor cells induces histological and motor improvements in a rat model of Parkinson’s disease: hNPCs secretome for Parkinson’s disease repair. STEM CELLS Translational Medicine [Internet]; 2018 [cited 2018 Oct 2]. Available from: http://doi.wiley.com/10.1002/sctm.18-0009.
   Google Scholar
• Polazzi E, Altamira LEP, Eleuteri S, et al. Neuroprotection of microglial conditioned medium on 6-hydroxydopamine-induced neuronal death: role of transforming growth factor beta-2. J Neurochem. 2009;110:545–556.
   PubMed Web of Science ®Google Scholar
• Feng L, Meng H, Wu F, et al. Olfactory ensheathing cells conditioned medium prevented apoptosis induced by 6-OHDA in PC12 cells through modulation of intrinsic apoptotic pathways. Int J Dev Neurosci. 2008;26:323–329.
   PubMed Web of Science ®Google Scholar
• Safi R, Gardaneh M, Panahi Y, et al. Optimized quantities of GDNF overexpressed by engineered astrocytes are critical for protection of neuroblastoma cells against 6-OHDA toxicity. J Mol Neurosci. 2012;46:654–665.
   PubMed Web of Science ®Google Scholar
• Biju KC, Santacruz RA, Chen C, et al. Bone marrow-derived microglia-based neurturin delivery protects against dopaminergic neurodegeneration in a mouse model of Parkinson’s disease. Neurosci Lett. 2013;535:24–29.
   PubMed Web of Science ®Google Scholar
• Liu Q, Qin Q, Sun H, et al. Neuroprotective effect of olfactory ensheathing cells co-transfected with Nurr1 and Ngn2 in both in vitro and in vivo models of Parkinson’s disease. Life Sci. 2018;194:168–176.
   PubMed Web of Science ®Google Scholar
• Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98:1076–1084.
   PubMed Web of Science ®Google Scholar
• Weiss ML, Medicetty S, Bledsoe AR, et al. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells. 2006;24:781–792.
   PubMed Web of Science ®Google Scholar
• Cova L, Armentero M-T, Zennaro E, et al. Multiple neurogenic and neurorescue effects of human mesenchymal stem cell after transplantation in an experimental model of Parkinson’s disease. Brain Res. 2010;1311:12–27.
   PubMed Web of Science ®Google Scholar
• Wang F, Yasuhara T, Shingo T, et al. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: focusing on neuroprotective effects of stromal cell-derived factor-1α. BMC Neurosci. 2010;11:52.
   PubMed Web of Science ®Google Scholar
• Teixeira FG, Carvalho MM, Neves-Carvalho A, et al. Secretome of mesenchymal progenitors from the umbilical cord acts as modulator of neural/glial proliferation and differentiation. Stem Cell Rev Rep. 2015;11:288–297.
   PubMed Web of Science ®Google Scholar
• Cova L, Bossolasco P, Armentero M-T, et al. Neuroprotective effects of human mesenchymal stem cells on neural cultures exposed to 6-hydroxydopamine: implications for reparative therapy in Parkinson’s disease. Apoptosis. 2012;17:289–304.
   PubMed Web of Science ®Google Scholar
• Yalvaç ME, Yarat A, Mercan D, et al. Characterization of the secretome of human tooth germ stem cells (hTGSCs) reveals neuro-protection by fine-tuning micro-environment. Brain Behav Immun. 2013;32:122–130.
   PubMed Web of Science ®Google Scholar
• Parga JA, García-Garrote M, Martínez S, et al. Prostaglandin EP2 receptors mediate mesenchymal stromal cell-neuroprotective effects on dopaminergic neurons. Mol Neurobiol. 2018;55:4763–4776.
   PubMed Web of Science ®Google Scholar
• Teixeira FG, Carvalho MM, Panchalingam KM, et al. 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 Transl Med. 2017;6:634–646.
   PubMed Web of Science ®Google Scholar
• Oh SH, Kim HN, Park HJ, et al. The cleavage effect of mesenchymal stem cell and its derived matrix metalloproteinase-2 on extracellular α-synuclein aggregates in Parkinsonian models. Stem Cells Transl Med. 2017;6:949–961.
   PubMed Web of Science ®Google Scholar
• Shintani A, Nakao N, Kakishita K, et al. Protection of dopamine neurons by bone marrow stromal cells. Brain Res. 2007;1186:48–55.
   PubMed Web of Science ®Google Scholar
• Yao Y, Huang C, Gu P, et al. Combined MSC-secreted factors and neural stem cell transplantation promote functional recovery of PD Rats. Cell Transplant. 2016;25:1101–1113.
   PubMed Web of Science ®Google Scholar
• Marote A, Teixeira FG, Mendes-Pinheiro B, et al. MSCs-derived exosomes: cell-secreted nanovesicles with regenerative potential. Front Pharmacol. 2016;7:231.
   PubMed Web of Science ®Google Scholar
• Jarmalavičiūtė A, Tunaitis V, Pivoraitė U, et al. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine–induced apoptosis. Cytotherapy. 2015;17:932–939.
   PubMed Web of Science ®Google Scholar
• Sadan O, Bahat-Stromza M, Barhum Y, et al. Protective effects of neurotrophic factor–secreting cells in a 6-OHDA rat model of Parkinson disease. Stem Cells Dev. 2009;18:1179–1190.
   PubMed Web of Science ®Google Scholar
• Moloney TC, Rooney GE, Barry FP, et al. Potential of rat bone marrow-derived mesenchymal stem cells as vehicles for delivery of neurotrophins to the Parkinsonian rat brain. Brain Res. 2010;1359:33–43.
   PubMed Web of Science ®Google Scholar
• Hoban DB, Howard L, Dowd E. GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson’s disease. Neuroscience. 2015;303:402–411.
   PubMed Web of Science ®Google Scholar
• Liu X-S, Li J-F, Wang -S-S, et al. Human umbilical cord mesenchymal stem cells infected with adenovirus expressing HGF promote regeneration of damaged neuron cells in a Parkinson’s disease model. Biomed Res Int. 2014;2014:909657.
   PubMedGoogle Scholar
• Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther. 2007;9:204.
   PubMed Web of Science ®Google Scholar
• Jung S, Teixeira FG, Panchalingam KM, et al. Potential therapeutic properties of human mesenchymal stem cells. J Clin Stud. 2012;4:36–40.
   Google Scholar
• Abdi R, Fiorina P, Adra CN, et al. Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes. 2008;57:1759–1767.
   PubMed Web of Science ®Google Scholar
• Bonfield TL, Nolan Koloze MT, Lennon DP, et al. Defining human mesenchymal stem cell efficacy in vivo. J Inflamm (Lond). 2010;7:51.
   PubMed Web of Science ®Google Scholar
• Chen Y, Shao J-Z, Xiang L-X, et al. Mesenchymal stem cells: a promising candidate in regenerative medicine. Int J Biochem Cell Biol. 2008;40:815–820.
   PubMed Web of Science ®Google Scholar
• Silva NA, Moreira J, Ribeiro-Samy S, et al. Modulation of bone marrow mesenchymal stem cell secretome by ECM-like hydrogels. Biochimie. 2013;95:2314–2319.
   PubMed Web of Science ®Google Scholar
• Oh SH, Lee SC, Kim DY, et al. Mesenchymal stem cells stabilize axonal transports for autophagic clearance of α-synuclein in Parkinsonian models. Stem Cells. 2017;35:1934–1947.
   PubMed Web of Science ®Google Scholar
• Jung S, Panchalingam KM, Wuerth RD, et al. Large-scale production of human mesenchymal stem cells for clinical applications. Biotechnol Appl Biochem. 2012;59:106–120.
   PubMed Web of Science ®Google Scholar
• Kusuma GD, Carthew J, Lim R, et al. Effect of the microenvironment on mesenchymal stem cell paracrine signaling: opportunities to engineer the therapeutic effect. Stem Cells Dev. 2017;26:617–631.
   PubMed Web of Science ®Google Scholar
• Sart S, Agathos SN, Li Y, et al. Regulation of mesenchymal stem cell 3D microenvironment: from macro to microfluidic bioreactors. Biotechnol J. 2016;11:43–57.
   PubMed Web of Science ®Google Scholar
• Jagannathan L, Cuddapah S, Costa M. Oxidative stress under ambient and physiological oxygen tension in tissue culture. Current Pharmacol Rep. 2016;2:64–72.
   PubMedGoogle Scholar
• Palumbo S, Tsai T-L, Li W-J. Macrophage migration inhibitory factor regulates AKT signaling in hypoxic culture to modulate senescence of human mesenchymal stem cells. Stem Cells Dev. 2014;23:852–865.
   PubMed Web of Science ®Google Scholar
• Zhang L, Yang J, Tian Y-M, et al. Beneficial effects of hypoxic preconditioning on human umbilical cord mesenchymal stem cells. Chin J Physiol. 2015;58:343–353.
   PubMed Web of Science ®Google Scholar
• Zhuo Y, Wang L, Ge L, et al. Hypoxic culture promotes dopaminergic-neuronal differentiation of nasal olfactory mucosa mesenchymal stem cells via upregulation of hypoxia-inducible factor-1α. Cell Transplant. 2017;26:1452–1461.
   PubMed Web of Science ®Google Scholar
• Liu L, Gao J, Yuan Y, et al. Hypoxia preconditioned human adipose derived mesenchymal stem cells enhance angiogenic potential via secretion of increased VEGF and bFGF. Cell Biol Int. 2013;37:551–560.
   PubMed Web of Science ®Google Scholar
• Teixeira FG, Panchalingam KM, Anjo SI, et al. Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of Wharton Jelly mesenchymal stem cell secretome? Stem Cell Res Ther. 2015;6:133.
   PubMed Web of Science ®Google Scholar
• Yuan T, Zhuo Y, Su C, et al. Hypoxic and ischemic effects on gene and protein expression levels of paracrine factors by human olfactory mucosa mesenchymal-like stem cells. J Neurorestoratol. 2016;4:85–94.
   Web of Science ®Google Scholar
• Ahmed NE-MB, Murakami M, Kaneko S, et al. The effects of hypoxia on the stemness properties of human dental pulp stem cells (DPSCs). Sci Rep. 2016;6:35476.
   PubMed Web of Science ®Google Scholar
• Chang C-P, Chio -C-C, Cheong C-U, et al. Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury. Clin Sci. 2013;124:165–176.
   PubMed Web of Science ®Google Scholar
• Panchalingam KM, Jung S, Rosenberg L, et al. Bioprocessing strategies for the large-scale production of human mesenchymal stem cells: a review. Stem Cell Res Ther. 2015;6:225.
   PubMed Web of Science ®Google Scholar
• Tandon N, Marolt D, Cimetta E, et al. Bioreactor engineering of stem cell environments. Biotechnol Adv. 2013;31:1020–1031.
   PubMed Web of Science ®Google Scholar
• Grad S, Eglin D, Alini M, et al. Physical stimulation of chondrogenic cells in vitro: a review. Clin Orthop Relat Res. 2011;469:2764–2772.
   PubMed Web of Science ®Google Scholar
• Cochis A, Grad S, Stoddart MJ, et al. Bioreactor mechanically guided 3D mesenchymal stem cell chondrogenesis using a biocompatible novel thermo-reversible methylcellulose-based hydrogel. Sci Rep. 2017;7:45018.
   PubMed Web of Science ®Google Scholar
• Agrawal P, Pramanik K, Biswas A, et al. In vitro cartilage construct generation from silk fibroin- chitosan porous scaffold and umbilical cord blood derived human mesenchymal stem cells in dynamic culture condition. J Biomed Mater Res A. 2018;106:397–407.
   PubMed Web of Science ®Google Scholar
• Stefani I, Asnaghi MA, Cooper-White JJ, et al. A double chamber rotating bioreactor for enhanced tubular tissue generation from human mesenchymal stem cells: a promising tool for vascular tissue regeneration. J Tissue Eng Regen Med. 2018;12:e42–e52.
   PubMed Web of Science ®Google Scholar
• King JA, Miller WM. Bioreactor development for stem cell expansion and controlled differentiation. Curr Opin Chem Biol. 2007;11:394–398.
   PubMed Web of Science ®Google Scholar
• Hupfeld J, Gorr IH, Schwald C, et al. Modulation of mesenchymal stromal cell characteristics by microcarrier culture in bioreactors. Biotechnol Bioeng. 2014;111:2290–2302.
   PubMed Web of Science ®Google Scholar
• Teixeira FG, Panchalingam KM, Assunção-Silva R, et al. Modulation of the mesenchymal stem cell secretome using computer-controlled bioreactors: impact on neuronal cell proliferation, survival and differentiation. Sci Rep. 2016;6:27791.
   PubMed Web of Science ®Google Scholar
• Chierchia A, Chirico N, Boeri L, et al. Secretome released from hydrogel-embedded adipose mesenchymal stem cells protects against the Parkinson’s disease related toxin 6-hydroxydopamine. Eur J Pharm Biopharm. 2017;121:113–120.
   PubMed Web of Science ®Google Scholar
• Grandhi R, Ricks C, Shin S, et al. Extracellular matrices, artificial neural scaffolds and the promise of neural regeneration. Neural Regen Res. 2014;9:1573.
   PubMed Web of Science ®Google Scholar
• Chien H-W, Fu S-W, Shih A-Y, et al. Modulation of the stemness and osteogenic differentiation of human mesenchymal stem cells by controlling RGD concentrations of poly(carboxybetaine) hydrogel. Biotechnol J. 2014;9:1613–1623.
   PubMed Web of Science ®Google Scholar
• Lee JH, Lee J-Y, Yang SH, et al. Carbon nanotube–collagen three-dimensional culture of mesenchymal stem cells promotes expression of neural phenotypes and secretion of neurotrophic factors. Acta Biomater. 2014;10:4425–4436.
   PubMed Web of Science ®Google Scholar
• Gugliandolo A, Diomede F, Cardelli P, et al. Transcriptomic analysis of gingival mesenchymal stem cells cultured on 3D bioprinted scaffold: a promising strategy for neuroregeneration. J Biomed Mater Res A. 2018;106:126–137.
   PubMed Web of Science ®Google Scholar
• Vunjak-Novakovic G, Scadden DT. Biomimetic platforms for human stem cell research. Cell Stem Cell. 2011;8:252–261.
   PubMed Web of Science ®Google Scholar
• McKee C, Chaudhry GR. Advances and challenges in stem cell culture. Colloids Surf B Biointerfaces. 2017;159:62–77.
   PubMed Web of Science ®Google Scholar
• Yamaguchi Y, Ohno J, Sato A, et al. Mesenchymal stem cell spheroids exhibit enhanced in-vitro and in-vivo osteoregenerative potential. BMC Biotechnol. 2014;14:105.
   PubMed Web of Science ®Google Scholar
• Murphy KC, Whitehead J, Falahee PC, et al. Multifactorial experimental design to optimize the anti-inflammatory and proangiogenic potential of mesenchymal stem cell spheroids. Stem Cells. 2017;35:1493–1504.
   PubMed Web of Science ®Google Scholar
• Lee JH, Han Y-S, Lee SH. Long-duration three-dimensional spheroid culture promotes angiogenic activities of adipose-derived mesenchymal stem cells. Biomol Ther (Seoul). 2016;24:260–267.
   PubMed Web of Science ®Google Scholar
• Xu Y, Shi T, Xu A, et al. 3D spheroid culture enhances survival and therapeutic capacities of MSCs injected into ischemic kidney. J Cell Mol Med. 2016;20:1203–1213.
   PubMed Web of Science ®Google Scholar
• Redondo-Castro E, Cunningham CJ, Miller J, et al. Changes in the secretome of tri-dimensional spheroid-cultured human mesenchymal stem cells in vitro by interleukin-1 priming. Stem Cell Res Ther. 2018;9:11.
   PubMed Web of Science ®Google Scholar
• Berg J, Roch M, Altschüler J, et al. Human adipose-derived mesenchymal stem cells improve motor functions and are neuroprotective in the 6-hydroxydopamine-rat model for Parkinson’s disease when cultured in monolayer cultures but suppress hippocampal neurogenesis and hippocampal memory functi. Stem Cell Rev Rep. 2015;11:133–149.
   PubMed Web of Science ®Google Scholar
• Gopalakrishna A, Alexander SA. Understanding Parkinson disease. J Neurosci Nurs. 2015;47:320–326.
   PubMed Web of Science ®Google Scholar
• Cacabelos R. Parkinson’s disease: from pathogenesis to pharmacogenomics. Int J Mol Sci. 2017;18:551.
   PubMed Web of Science ®Google Scholar
• Shafiq M, Jung Y, Kim SH. Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair. Biomaterials. 2016;90:85–115.
   PubMed Web of Science ®Google Scholar
• Du Y, Li X, Yang D, et al. Multiple molecular pathways are involved in the neuroprotection of GDNF against proteasome inhibitor induced dopamine neuron degeneration in vivo. Exp Biol Med. 2008;233:881–890.
   Web of Science ®Google Scholar
• Oh SE, Park H-J, He L, et al. The Parkinson’s disease gene product DJ-1 modulates miR-221 to promote neuronal survival against oxidative stress. Redox Biol. 2018;19:62–73.
   PubMed Web of Science ®Google Scholar
• Falk T, Gonzalez RT, Sherman SJ. The Yin and Yang of VEGF and PEDF: multifaceted neurotrophic factors and their potential in the treatment of Parkinson’s disease. Int J Mol Sci. 2010;11:2875–2900.
   PubMed Web of Science ®Google Scholar
• Zou J, Chen Z, Wei X, et al. Cystatin C as a potential therapeutic mediator against Parkinson’s disease via VEGF-induced angiogenesis and enhanced neuronal autophagy in neurovascular units. Cell Death Dis. 2017;8:e2854.
   PubMed Web of Science ®Google Scholar
• Pires AO, Mendes-Pinheiro B, Teixeira FG, et al. Unveiling the differences of secretome of human bone marrow mesenchymal stem cells, adipose tissue-derived stem cells, and human umbilical cord perivascular cells: a proteomic analysis. Stem Cells Dev. 2016;25:1073–1083.
   PubMed Web of Science ®Google Scholar
• Yasuhara T, Shingo T, Kobayashi K, et al. Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson’s disease. Eur J Neurosci. 2004;19:1494–1504.
   PubMed Web of Science ®Google Scholar
• Hirano T, Ishihara K, Hibi M. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene. 2000;19:2548–2556.
   PubMed Web of Science ®Google Scholar
• Wong YC, Krainc D. α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies. Nat Med. 2017;23:1–13.
   PubMed Web of Science ®Google Scholar
• Park HJ, Oh SH, Kim HN, et al. Mesenchymal stem cells enhance α-synuclein clearance via M2 microglia polarization in experimental and human parkinsonian disorder. Acta Neuropathol. 2016;132:685–701.
   PubMed Web of Science ®Google Scholar