A Cellular Model of Amyotrophic Lateral Sclerosis to Study the Therapeutic Effects of Extracellular Vesicles from Adipose Mesenchymal Stem Cells on Microglial Activation
Abstract
:1. Introduction
2. Results
2.1. Doxycycline Induces the Expression of hSOD1(G93A) in Microglial Cells
2.2. hSOD1(G93A) Protein Is Able to Induce Microglial Activation
2.3. hSOD1(G93A) Expression Reveals Morphological Changes Phenotype in Microglial Cells
2.4. hSOD1(G93A) Expression Triggers a Detrimental Phenotype in Microglial Cells
2.5. Characterization of ASC-EVs
2.6. ASC-EVs Are Able to Reduce the Activation of Microglial Cells
2.7. ASC-EVs Are Able to Modulate the Phenotype of Microglial Cells
2.8. ASC-EVs Are Able to Reduce ROS Release by Microglial Cells
3. Discussion
4. Materials and Methods
4.1. Cell Cultures
4.2. Western Blot
4.3. ASC-EV Isolation and Characterization
4.4. WST Assay
4.5. The Enzyme-Linked Immunospot Assay (ELISpot)
4.6. Morphological Characterization of SIM-A9hSOD1(G93A) Cells
4.7. Immunofluorescence Staining
4.8. Flow Cytometry
4.9. ROS Evaluation
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Abati, E.; Bresolin, N.; Comi, G.; Corti, S. Silence superoxide dismutase 1 (SOD1): A promising therapeutic target for amyotrophic lateral sclerosis (ALS). Expert Opin. Ther. Targets 2020, 24, 295–310. [Google Scholar] [CrossRef] [PubMed]
- Bonafede, R.; Mariotti, R. ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles. Front. Cell Neurosci. 2017, 11, 80. [Google Scholar] [CrossRef] [PubMed]
- Jaiswal, M.K. Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs. Med. Res. Rev. 2019, 39, 733–748. [Google Scholar] [CrossRef] [PubMed]
- Clarke, B.E.; Gil, R.S.; Yip, J.; Kalmar, B.; Greensmith, L. Regional differences in the inflammatory and heat shock response in glia: Implications for ALS. Cell Stress Chaperones 2019, 24, 857–870. [Google Scholar] [CrossRef] [PubMed]
- McCauley, M.E.; Baloh, R.H. Inflammation in ALS/FTD pathogenesis. Acta Neuropathol. 2019, 137, 715–730. [Google Scholar] [CrossRef]
- van Es, M.A.; Hardiman, O.; Chio, A.; Al-Chalabi, A.; Pasterkamp, R.J.; Veldink, J.H.; van den Berg, L.H. Amyotrophic lateral sclerosis. Lancet 2017, 390, 2084–2098. [Google Scholar] [CrossRef] [PubMed]
- Deora, V.; Lee, J.D.; Albornoz, E.A.; McAlary, L.; Jagaraj, C.J.; Robertson, A.A.B.; Atkin, J.D.; Cooper, M.A.; Schroder, K.; Yerbury, J.J.; et al. The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins. Glia 2020, 68, 407–421. [Google Scholar] [CrossRef] [PubMed]
- Haukedal, H.; Freude, K. Implications of Microglia in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. J. Mol. Biol. 2019, 431, 1818–1829. [Google Scholar] [CrossRef] [PubMed]
- Jara, J.H.; Gautam, M.; Kocak, N.; Xie, E.F.; Mao, Q.; Bigio, E.H.; Ozdinler, P.H. MCP1-CCR2 and neuroinflammation in the ALS motor cortex with TDP-43 pathology. J. Neuroinflamm. 2019, 16, 196. [Google Scholar] [CrossRef]
- Migliarini, S.; Scaricamazza, S.; Valle, C.; Ferri, A.; Pasqualetti, M.; Ferraro, E. Microglia Morphological Changes in the Motor Cortex of hSOD1(G93A) Transgenic ALS Mice. Brain Sci. 2021, 11, 807. [Google Scholar] [CrossRef]
- Filipi, T.; Hermanova, Z.; Tureckova, J.; Vanatko, O.; Anderova, A.M. Glial Cells-The Strategic Targets in Amyotrophic Lateral Sclerosis Treatment. J. Clin. Med. 2020, 9, 261. [Google Scholar] [CrossRef] [PubMed]
- Jurga, A.M.; Paleczna, M.; Kuter, K.Z. Overview of General and Discriminating Markers of Differential Microglia Phenotypes. Front. Cell Neurosci. 2020, 14, 198. [Google Scholar] [CrossRef] [PubMed]
- Liddelow, S.A.; Barres, B.A. Reactive Astrocytes: Production, Function, and Therapeutic Potential. Immunity 2017, 46, 957–967. [Google Scholar] [CrossRef] [PubMed]
- Tang, Y.; Le, W. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases. Mol. Neurobiol. 2016, 53, 1181–1194. [Google Scholar] [CrossRef]
- Zhao, W.; Beers, D.R.; Appel, S.H. Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis. J. Neuroimmune Pharmacol. 2013, 8, 888–899. [Google Scholar] [CrossRef]
- Brites, D.; Vaz, A.R. Microglia centered pathogenesis in ALS: Insights in cell interconnectivity. Front. Cell Neurosci. 2014, 8, 117. [Google Scholar] [CrossRef] [PubMed]
- Greco, V.; Longone, P.; Spalloni, A.; Pieroni, L.; Urbani, A. Crosstalk Between Oxidative Stress and Mitochondrial Damage: Focus on Amyotrophic Lateral Sclerosis. Adv. Exp. Med. Biol. 2019, 1158, 71–82. [Google Scholar] [CrossRef]
- Agar, J.; Durham, H. Relevance of oxidative injury in the pathogenesis of motor neuron diseases. Amyotroph. Lateral. Scler. Other Mot. Neuron. Disord. 2003, 4, 232–242. [Google Scholar] [CrossRef] [PubMed]
- Golpich, M.; Amini, E.; Mohamed, Z.; Azman Ali, R.; Mohamed Ibrahim, N.; Ahmadiani, A. Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment. CNS Neurosci. Ther. 2017, 23, 5–22. [Google Scholar] [CrossRef]
- Singh, A.; Kukreti, R.; Saso, L.; Kukreti, S. Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules 2019, 24, 1583. [Google Scholar] [CrossRef]
- Baloh, R.H.; Glass, J.D.; Svendsen, C.N. Stem cell transplantation for amyotrophic lateral sclerosis. Curr. Opin. Neurol. 2018, 31, 655–661. [Google Scholar] [CrossRef] [PubMed]
- Mazzini, L.; Vescovi, A.; Cantello, R.; Gelati, M.; Vercelli, A. Stem cells therapy for ALS. Expert. Opin. Biol. Ther. 2016, 16, 187–199. [Google Scholar] [CrossRef] [PubMed]
- Dabrowska, S.; Sypecka, J.; Jablonska, A.; Strojek, L.; Wielgos, M.; Domanska-Janik, K.; Sarnowska, A. Neuroprotective Potential and Paracrine Activity of Stromal Vs. Culture-Expanded hMSC Derived from Wharton Jelly under Co-Cultured with Hippocampal Organotypic Slices. Mol. Neurobiol. 2018, 55, 6021–6036. [Google Scholar] [CrossRef] [PubMed]
- Kachgal, S.; Putnam, A.J. Mesenchymal stem cells from adipose and bone marrow promote angiogenesis via distinct cytokine and protease expression mechanisms. Angiogenesis 2011, 14, 47–59. [Google Scholar] [CrossRef] [PubMed]
- Koniusz, S.; Andrzejewska, A.; Muraca, M.; Srivastava, A.K.; Janowski, M.; Lukomska, B. Extracellular Vesicles in Physiology, Pathology, and Therapy of the Immune and Central Nervous System, with Focus on Extracellular Vesicles Derived from Mesenchymal Stem Cells as Therapeutic Tools. Front. Cell Neurosci. 2016, 10, 109. [Google Scholar] [CrossRef] [PubMed]
- Davidson, S.M.; Takov, K.; Yellon, D.M. Exosomes and Cardiovascular Protection. Cardiovasc. Drugs Ther. 2017, 31, 77–86. [Google Scholar] [CrossRef] [PubMed]
- Pan, W.; Zhu, Y.; Meng, X.; Zhang, C.; Yang, Y.; Bei, Y. Immunomodulation by Exosomes in Myocardial Infarction. J. Cardiovasc. Transl. Res. 2019, 12, 28–36. [Google Scholar] [CrossRef] [PubMed]
- Armesilla-Diaz, A.; Elvira, G.; Silva, A. p53 regulates the proliferation, differentiation and spontaneous transformation of mesenchymal stem cells. Exp. Cell Res. 2009, 315, 3598–3610. [Google Scholar] [CrossRef] [PubMed]
- Eliopoulos, N.; Stagg, J.; Lejeune, L.; Pommey, S.; Galipeau, J. Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood 2005, 106, 4057–4065. [Google Scholar] [CrossRef]
- Gleeson, B.M.; Martin, K.; Ali, M.T.; Kumar, A.H.; Pillai, M.G.; Kumar, S.P.; O’Sullivan, J.F.; Whelan, D.; Stocca, A.; Khider, W.; et al. Bone Marrow-Derived Mesenchymal Stem Cells Have Innate Procoagulant Activity and Cause Microvascular Obstruction Following Intracoronary Delivery: Amelioration by Antithrombin Therapy. Stem Cells 2015, 33, 2726–2737. [Google Scholar] [CrossRef]
- Chen, H.X.; Liang, F.C.; Gu, P.; Xu, B.L.; Xu, H.J.; Wang, W.T.; Hou, J.Y.; Xie, D.X.; Chai, X.Q.; An, S.J. Exosomes derived from mesenchymal stem cells repair a Parkinson’s disease model by inducing autophagy. Cell Death Dis. 2020, 11, 288. [Google Scholar] [CrossRef] [PubMed]
- Dabrowska, S.; Andrzejewska, A.; Lukomska, B.; Janowski, M. Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles. J. Neuroinflamm. 2019, 16, 178. [Google Scholar] [CrossRef] [PubMed]
- Ding, M.; Shen, Y.; Wang, P.; Xie, Z.; Xu, S.; Zhu, Z.; Wang, Y.; Lyu, Y.; Wang, D.; Xu, L.; et al. Exosomes Isolated From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Neuroinflammation and Reduce Amyloid-Beta Deposition by Modulating Microglial Activation in Alzheimer’s Disease. Neurochem. Res. 2018, 43, 2165–2177. [Google Scholar] [CrossRef]
- Li, Z.; Liu, F.; He, X.; Yang, X.; Shan, F.; Feng, J. Exosomes derived from mesenchymal stem cells attenuate inflammation and demyelination of the central nervous system in EAE rats by regulating the polarization of microglia. Int. Immunopharmacol. 2019, 67, 268–280. [Google Scholar] [CrossRef] [PubMed]
- Turano, E.; Scambi, I.; Bonafede, R.; Dusi, S.; Angelini, G.; Lopez, N.; Marostica, G.; Rossi, B.; Furlan, R.; Constantin, G.; et al. Extracellular vescicles from adipose mesenchymal stem cells target inflamed lymph nodes in experimental autoimmune encephalomyelitis. Cytotherapy 2024, 26, 276–285. [Google Scholar] [CrossRef]
- Bonafede, R.; Turano, E.; Scambi, I.; Busato, A.; Bontempi, P.; Virla, F.; Schiaffino, L.; Marzola, P.; Bonetti, B.; Mariotti, R. ASC-Exosomes Ameliorate the Disease Progression in SOD1(G93A) Murine Model Underlining Their Potential Therapeutic Use in Human ALS. Int. J. Mol. Sci. 2020, 21, 3651. [Google Scholar] [CrossRef]
- Bonafede, R.; Scambi, I.; Peroni, D.; Potrich, V.; Boschi, F.; Benati, D.; Bonetti, B.; Mariotti, R. Exosome derived from murine adipose-derived stromal cells: Neuroprotective effect on in vitro model of amyotrophic lateral sclerosis. Exp. Cell Res. 2016, 340, 150–158. [Google Scholar] [CrossRef] [PubMed]
- Nagamoto-Combs, K.; Kulas, J.; Combs, C.K. A novel cell line from spontaneously immortalized murine microglia. J. Neurosci. Methods 2014, 233, 187–198. [Google Scholar] [CrossRef]
- Calabria, E.; Scambi, I.; Bonafede, R.; Schiaffino, L.; Peroni, D.; Potrich, V.; Capelli, C.; Schena, F.; Mariotti, R. ASCs-Exosomes Recover Coupling Efficiency and Mitochondrial Membrane Potential in an in vitro Model of ALS. Front. Neurosci. 2019, 13, 1070. [Google Scholar] [CrossRef]
- Doyle, L.M.; Wang, M.Z. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells 2019, 8, 727. [Google Scholar] [CrossRef]
- Masrori, P.; Van Damme, P. Amyotrophic lateral sclerosis: A clinical review. Eur. J. Neurol. 2020, 27, 1918–1929. [Google Scholar] [CrossRef]
- Beers, D.R.; Appel, S.H. Immune dysregulation in amyotrophic lateral sclerosis: Mechanisms and emerging therapies. Lancet Neurol. 2019, 18, 211–220. [Google Scholar] [CrossRef]
- Di Giorgio, F.P.; Carrasco, M.A.; Siao, M.C.; Maniatis, T.; Eggan, K. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat. Neurosci. 2007, 10, 608–614. [Google Scholar] [CrossRef] [PubMed]
- Chiot, A.; Zaïdi, S.; Iltis, C.; Ribon, M.; Berriat, F.; Schiaffino, L.; Jolly, A.; de la Grange, P.; Mallat, M.; Bohl, D.; et al. Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival. Nat. Neurosci. 2020, 23, 1339–1351. [Google Scholar] [CrossRef]
- Frakes, A.E.; Ferraiuolo, L.; Haidet-Phillips, A.M.; Schmelzer, L.; Braun, L.; Miranda, C.J.; Ladner, K.J.; Bevan, A.K.; Foust, K.D.; Godbout, J.P.; et al. Microglia induce motor neuron death via the classical NF-kappaB pathway in amyotrophic lateral sclerosis. Neuron 2014, 81, 1009–1023. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.C.; Seong, J.; Kim, S.H.; Lee, S.J.; Cho, Y.J.; An, J.; Nam, D.H.; Joo, K.M.; Cha, C.I. Replacement of microglial cells using Clodronate liposome and bone marrow transplantation in the central nervous system of SOD1(G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun. 2012, 418, 359–365. [Google Scholar] [CrossRef] [PubMed]
- Dahlke, C.; Saberi, D.; Ott, B.; Brand-Saberi, B.; Schmitt-John, T.; Theiss, C. Inflammation and neuronal death in the motor cortex of the wobbler mouse, an ALS animal model. J. Neuroinflamm. 2015, 12, 215. [Google Scholar] [CrossRef]
- Gois, A.M.; Mendonça, D.M.F.; Freire, M.A.M.; Santos, J.R. IN VITRO AND IN VIVO MODELS OF AMYOTROPHIC LATERAL SCLEROSIS: AN UPDATED OVERVIEW. Brain Res. Bull. 2020, 159, 32–43. [Google Scholar] [CrossRef] [PubMed]
- Guidotti, G.; Scarlata, C.; Brambilla, L.; Rossi, D. Tumor Necrosis Factor Alpha in Amyotrophic Lateral Sclerosis: Friend or Foe? Cells 2021, 10, 518. [Google Scholar] [CrossRef]
- Hensley, K.; Fedynyshyn, J.; Ferrell, S.; Floyd, R.A.; Gordon, B.; Grammas, P.; Hamdheydari, L.; Mhatre, M.; Mou, S.; Pye, Q.N.; et al. Message and protein-level elevation of tumor necrosis factor alpha (TNF alpha) and TNF alpha-modulating cytokines in spinal cords of the G93A-SOD1 mouse model for amyotrophic lateral sclerosis. Neurobiol. Dis. 2003, 14, 74–80. [Google Scholar] [CrossRef]
- Massenzio, F.; Peña-Altamira, E.; Petralla, S.; Virgili, M.; Zuccheri, G.; Miti, A.; Polazzi, E.; Mengoni, I.; Piffaretti, D.; Monti, B. Microglial overexpression of fALS-linked mutant SOD1 induces SOD1 processing impairment, activation and neurotoxicity and is counteracted by the autophagy inducer trehalose. Biochim. Biophys. Acta Mol. Basis Dis. 2018, 1864, 3771–3785. [Google Scholar] [CrossRef] [PubMed]
- Kraft, A.D.; Resch, J.M.; Johnson, D.A.; Johnson, J.A. Activation of the Nrf2-ARE pathway in muscle and spinal cord during ALS-like pathology in mice expressing mutant SOD1. Exp. Neurol. 2007, 207, 107–117. [Google Scholar] [CrossRef] [PubMed]
- Vande Velde, C.; McDonald, K.K.; Boukhedimi, Y.; McAlonis-Downes, M.; Lobsiger, C.S.; Bel Hadj, S.; Zandona, A.; Julien, J.P.; Shah, S.B.; Cleveland, D.W. Misfolded SOD1 associated with motor neuron mitochondria alters mitochondrial shape and distribution prior to clinical onset. PLoS ONE 2011, 6, e22031. [Google Scholar] [CrossRef] [PubMed]
- Ullah, F.; Gamage, R.; Sen, M.K.; Gyengesi, E. The Effects of Modified Curcumin Preparations on Glial Morphology in Aging and Neuroinflammation. Neurochem. Res. 2022, 47, 813–824. [Google Scholar] [CrossRef] [PubMed]
- Ziebell, J.M.; Adelson, P.D.; Lifshitz, J. Microglia: Dismantling and rebuilding circuits after acute neurological injury. Metab Brain Dis. 2015, 30, 393–400. [Google Scholar] [CrossRef] [PubMed]
- Gill, E.L.; Raman, S.; Yost, R.A.; Garrett, T.J.; Vedam-Mai, V. l-Carnitine Inhibits Lipopolysaccharide-Induced Nitric Oxide Production of SIM-A9 Microglia Cells. ACS Chem. Neurosci. 2018, 9, 901–905. [Google Scholar] [CrossRef] [PubMed]
- Colonna, M.; Butovsky, O. Microglia Function in the Central Nervous System During Health and Neurodegeneration. Annu. Rev. Immunol. 2017, 35, 441–468. [Google Scholar] [CrossRef] [PubMed]
- Sica, A.; Mantovani, A. Macrophage plasticity and polarization: In vivo veritas. J. Clin. Investig. 2012, 122, 787–795. [Google Scholar] [CrossRef] [PubMed]
- Correale, J. The role of microglial activation in disease progression. Mult. Scler. 2014, 20, 1288–1295. [Google Scholar] [CrossRef] [PubMed]
- Colton, C.; Wilcock, D.M. Assessing activation states in microglia. CNS Neurol. Disord. Drug Targets 2010, 9, 174–191. [Google Scholar] [CrossRef]
- Du, R.H.; Sun, H.B.; Hu, Z.L.; Lu, M.; Ding, J.H.; Hu, G. Kir6.1/K-ATP channel modulates microglia phenotypes: Implication in Parkinson’s disease. Cell Death Dis. 2018, 9, 404. [Google Scholar] [CrossRef] [PubMed]
- Chiu, I.M.; Morimoto, E.T.; Goodarzi, H.; Liao, J.T.; O’Keeffe, S.; Phatnani, H.P.; Muratet, M.; Carroll, M.C.; Levy, S.; Tavazoie, S.; et al. A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Rep. 2013, 4, 385–401. [Google Scholar] [CrossRef] [PubMed]
- Crain, J.M.; Nikodemova, M.; Watters, J.J. Microglia express distinct M1 and M2 phenotypic markers in the postnatal and adult central nervous system in male and female mice. J. Neurosci. Res. 2013, 91, 1143–1151. [Google Scholar] [CrossRef] [PubMed]
- Olah, M.; Amor, S.; Brouwer, N.; Vinet, J.; Eggen, B.; Biber, K.; Boddeke, H.W. Identification of a microglia phenotype supportive of remyelination. Glia 2012, 60, 306–321. [Google Scholar] [CrossRef] [PubMed]
- Parisi, C.; Napoli, G.; Pelegrin, P.; Volonté, C. M1 and M2 Functional Imprinting of Primary Microglia: Role of P2X7 Activation and miR-125b. Mediat. Inflamm. 2016, 2016, 2989548. [Google Scholar] [CrossRef] [PubMed]
- Budoni, M.; Fierabracci, A.; Luciano, R.; Petrini, S.; Di Ciommo, V.; Muraca, M. The immunosuppressive effect of mesenchymal stromal cells on B lymphocytes is mediated by membrane vesicles. Cell Transpl. 2013, 22, 369–379. [Google Scholar] [CrossRef] [PubMed]
- Dabrowska, S.; Andrzejewska, A.; Strzemecki, D.; Muraca, M.; Janowski, M.; Lukomska, B. Human bone marrow mesenchymal stem cell-derived extracellular vesicles attenuate neuroinflammation evoked by focal brain injury in rats. J. Neuroinflamm. 2019, 16, 216. [Google Scholar] [CrossRef] [PubMed]
- Drommelschmidt, K.; Serdar, M.; Bendix, I.; Herz, J.; Bertling, F.; Prager, S.; Keller, M.; Ludwig, A.K.; Duhan, V.; Radtke, S.; et al. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury. Brain Behav. Immun. 2017, 60, 220–232. [Google Scholar] [CrossRef]
- Chen, Y.; Li, J.; Ma, B.; Li, N.; Wang, S.; Sun, Z.; Xue, C.; Han, Q.; Wei, J.; Zhao, R.C. MSC-derived exosomes promote recovery from traumatic brain injury via microglia/macrophages in rat. Aging (Albany NY) 2020, 12, 18274–18296. [Google Scholar] [CrossRef]
- Sun, X.; Shan, A.; Wei, Z.; Xu, B. Intravenous mesenchymal stem cell-derived exosomes ameliorate myocardial inflammation in the dilated cardiomyopathy. Biochem. Biophys. Res. Commun. 2018, 503, 2611–2618. [Google Scholar] [CrossRef]
- Thomi, G.; Surbek, D.; Haesler, V.; Joerger-Messerli, M.; Schoeberlein, A. Exosomes derived from umbilical cord mesenchymal stem cells reduce microglia-mediated neuroinflammation in perinatal brain injury. Stem Cell Res. Ther. 2019, 10, 105. [Google Scholar] [CrossRef] [PubMed]
- Zhai, L.; Shen, H.; Sheng, Y.; Guan, Q. ADMSC Exo-MicroRNA-22 improve neurological function and neuroinflammation in mice with Alzheimer’s disease. J. Cell Mol. Med. 2021, 25, 7513–7523. [Google Scholar] [CrossRef] [PubMed]
- Ni, H.; Yang, S.; Siaw-Debrah, F.; Hu, J.; Wu, K.; He, Z.; Yang, J.; Pan, S.; Lin, X.; Ye, H.; et al. Exosomes Derived From Bone Mesenchymal Stem Cells Ameliorate Early Inflammatory Responses Following Traumatic Brain Injury. Front. Neurosci. 2019, 13, 14. [Google Scholar] [CrossRef] [PubMed]
- Kobayashi, K.; Imagama, S.; Ohgomori, T.; Hirano, K.; Uchimura, K.; Sakamoto, K.; Hirakawa, A.; Takeuchi, H.; Suzumura, A.; Ishiguro, N.; et al. Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis. 2013, 4, e525. [Google Scholar] [CrossRef] [PubMed]
- Provenzano, F.; Nyberg, S.; Giunti, D.; Torazza, C.; Parodi, B.; Bonifacino, T.; Usai, C.; Kerlero de Rosbo, N.; Milanese, M.; Uccelli, A.; et al. Micro-RNAs Shuttled by Extracellular Vesicles Secreted from Mesenchymal Stem Cells Dampen Astrocyte Pathological Activation and Support Neuroprotection in In-Vitro Models of ALS. Cells 2022, 11, 3923. [Google Scholar] [CrossRef] [PubMed]
- Dominici, M.; Le Blanc, K.; Mueller, I.; Slaper-Cortenbach, I.; Marini, F.; Krause, D.; Deans, R.; Keating, A.; Prockop, D.; Horwitz, E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006, 8, 315–317. [Google Scholar] [CrossRef]
- Farinazzo, A.; Turano, E.; Marconi, S.; Bistaffa, E.; Bazzoli, E.; Bonetti, B. Murine adipose-derived mesenchymal stromal cell vesicles: In vitro clues for neuroprotective and neuroregenerative approaches. Cytotherapy 2015, 17, 571–578. [Google Scholar] [CrossRef] [PubMed]
- Peroni, D.; Scambi, I.; Pasini, A.; Lisi, V.; Bifari, F.; Krampera, M.; Rigotti, G.; Sbarbati, A.; Galie, M. Stem molecular signature of adipose-derived stromal cells. Exp. Cell Res. 2008, 314, 603–615. [Google Scholar] [CrossRef]
- Szabo, M.; Gulya, K. Development of the microglial phenotype in culture. Neuroscience 2013, 241, 280–295. [Google Scholar] [CrossRef]
Size of ASC-EV | |||||
Mean (nm) | Mode (nm) | SD (nm) | D10 (nm) | D50 (nm) | D90 (nm) |
195.2 ± 2.2 | 138.7 ± 4.7 | 88.8 ± 6.9 | 127.3 ± 1.0 | 170.4 ± 1.7 | 271.9 ± 2.5 |
Concentration of ASC-EV | |||||
Concentration (Particles/mL) | Concentration (Particles/Frame) | Concentration (Centers/Frame) | |||
4.11 × 109 ± 2.03 × 107 | 224.6 ± 1.1 | 201.5 ± 0.3 |
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Dabrowska, S.; Turano, E.; Scambi, I.; Virla, F.; Nodari, A.; Pezzini, F.; Galiè, M.; Bonetti, B.; Mariotti, R. A Cellular Model of Amyotrophic Lateral Sclerosis to Study the Therapeutic Effects of Extracellular Vesicles from Adipose Mesenchymal Stem Cells on Microglial Activation. Int. J. Mol. Sci. 2024, 25, 5707. https://doi.org/10.3390/ijms25115707
Dabrowska S, Turano E, Scambi I, Virla F, Nodari A, Pezzini F, Galiè M, Bonetti B, Mariotti R. A Cellular Model of Amyotrophic Lateral Sclerosis to Study the Therapeutic Effects of Extracellular Vesicles from Adipose Mesenchymal Stem Cells on Microglial Activation. International Journal of Molecular Sciences. 2024; 25(11):5707. https://doi.org/10.3390/ijms25115707
Chicago/Turabian StyleDabrowska, Sylwia, Ermanna Turano, Ilaria Scambi, Federica Virla, Alice Nodari, Francesco Pezzini, Mirco Galiè, Bruno Bonetti, and Raffaella Mariotti. 2024. "A Cellular Model of Amyotrophic Lateral Sclerosis to Study the Therapeutic Effects of Extracellular Vesicles from Adipose Mesenchymal Stem Cells on Microglial Activation" International Journal of Molecular Sciences 25, no. 11: 5707. https://doi.org/10.3390/ijms25115707