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Exosomes — beyond stem cells for restorative therapy in stroke and neurological injury

Zhang, Zheng Gang, Buller, Benjamin, Chopp, Michael·2019·Nature Reviews Neurology
DOI 10.1038/s41582-018-0126-4
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Abstract

Stroke is a leading cause of disability worldwide, and brain injuries devastate patients and their families, but currently no drugs on the market promote neurological recovery. Limited spontaneous recovery of function as a result of brain remodelling after stroke or injury does occur, and cell-based therapies have been used to promote these endogenous processes. Increasing evidence is demonstrating that the positive effects of such cell-based therapy are mediated by exosomes released from the administered cells and that the microRNA cargo in these exosomes is largely responsible for the therapeutic effects. This evidence raises the possibility that isolated exosomes could be used alone as a neurorestorative therapy and that these exosomes could be tailored to maximize clinical benefit. The potential of exosomes as a therapy for brain disorders is therefore being actively investigated. In this Review, we discuss the current knowledge of exosomes and advances in our knowledge of their effects on endogenous neurovascular remodelling events. We also consider the opportunities for exosome-based approaches to therapeutic amplification of brain repair and improvement of recovery after stroke, traumatic brain injury and other diseases in which neurorestoration could be a viable treatment strategy.

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Research works printed but not linked: 123

  1. Lackland, D. T. et al. Factors influencing the decline in stroke mortality: a statement from the American Heart Association/American Stroke Association. Stroke 45, 315–353 (2014).
  2. Duncan, P. W., Goldstein, L. B., Matchar, D., Divine, G. W. & Feussner, J. Measurement of motor recovery after stroke. Outcome assessment and sample size requirements. Stroke 23, 1084–1089 (1992).
  3. Ueno, Y. et al. Axonal outgrowth and dendritic plasticity in the cortical peri-infarct area after experimental stroke. Stroke 43, 2221–2228 (2012). · DOI
  4. Li, Y., Liu, Z., Xin, H. & Chopp, M. The role of astrocytes in mediating exogenous cell-based restorative therapy for stroke. Glia 62, 1–16 (2014). · DOI
  5. Chen, J. et al. Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. J. Neurol. Sci. 189, 49–57 (2001). · DOI
  6. Chen, J. et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32, 1005–1011 (2001). · DOI
  7. Chopp, M. & Li, Y. Treatment of neural injury with marrow stromal cells. Lancet Neurol. 1, 92–100 (2002). · DOI
  8. Zhang, Y. et al. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. J. Neurosurgery 122, 856–867 (2015). · DOI · Paper page
  9. Xin, H. et al. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells 31, 2737–2746 (2013). · DOI
  10. Xin, H. et al. Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J. Cereb. Blood Flow Metab. 33, 1711–1715 (2013). · DOI
  11. Rak, J. Extracellular vesicles — biomarkers and effectors of the cellular interactome in cancer. Front. Pharmacol. 4, 21 (2013).
  12. Lener, T. et al. Applying extracellular vesicles based therapeutics in clinical trials — an ISEV position paper. J. Extracell. Vesicles 4, 30087 (2015). · DOI · Paper page
  13. Lai, C. P. & Breakefield, X. O. Role of exosomes/microvesicles in the nervous system and use in emerging therapies. Front. Physiol. 3, 228 (2012).
  14. Maas, S. L., Breakefield, X. O. & Weaver, A. M. Extracellular vesicles: unique intercellular delivery vehicles. Trends Cell Biol. 27, 172–188 (2017). · DOI
  15. Mateescu, B. et al. Obstacles and opportunities in the functional analysis of extracellular vesicle RNA — an ISEV position paper. J. Extracell. Vesicles 6, 1286095 (2017). · DOI
  16. Rufino-Ramos, D. et al. Extracellular vesicles: novel promising delivery systems for therapy of brain diseases. J. Control. Release 262, 247–258 (2017). · DOI · Paper page
  17. Mantel, P. Y. et al. Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria. Nat. Commun. 7, 12727 (2016). · DOI · Paper page
  18. Eacker, S. M., Dawson, T. M. & Dawson, V. L. Understanding microRNAs in neurodegeneration. Nat. Rev. Neurosci. 10, 837–841 (2009). · DOI · Paper page
  19. Macfarlane, L. A. & Murphy, P. R. MicroRNA: biogenesis, function and role in cancer. Curr. Genomics 11, 537–561 (2010). · DOI · Paper page
  20. Meister, G. Argonaute proteins: functional insights and emerging roles. Nat. Rev. Genet. 14, 447–459 (2013). · DOI
  21. Sempere, L. F., Cole, C. N., McPeek, M. A. & Peterson, K. J. The phylogenetic distribution of metazoan microRNAs: insights into evolutionary complexity and constraint. J. Exp. Zool. B 306, 575–588 (2006). · DOI
  22. Heimberg, A. M., Sempere, L. F., Moy, V. N., Donoghue, P. C. & Peterson, K. J. MicroRNAs and the advent of vertebrate morphological complexity. Proc. Natl Acad. Sci. USA 105, 2946–2950 (2008). · DOI
  23. Borroto-Escuela, D. O. et al. The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural-glial networks. Phil. Trans. R. Soc. B 370, 20140183 (2015). · DOI
  24. Banigan, M. G. et al. Differential expression of exosomal microRNAs in prefrontal cortices of schizophrenia and bipolar disorder patients. PLOS ONE 8, e48814 (2013). · DOI
  25. Basso, M. & Bonetto, V. Extracellular vesicles and a novel form of communication in the brain. Front. Neurosci. 10, 127 (2016). · DOI · Paper page
  26. Holm, M. M., Kaiser, J. & Schwab, M. E. Extracellular vesicles: multimodal envoys in neural maintenance and repair. Trends Neurosci. 41, 360–372 (2018). · DOI
  27. Lachenal, G. et al. Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Mol. Cell. Neurosci. 46, 409–418 (2011). · DOI
  28. Goldie, B. J. et al. Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons. Nucleic Acids Res. 42, 9195–9208 (2014). · DOI · Paper page
  29. Wang, S. et al. Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes. J. Neurosci. 31, 7275–7290 (2011). · DOI · Paper page
  30. Kramer-Albers, E. M. et al. Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: trophic support for axons? Proteomics Clin. Appl. 1, 1446–1461 (2007). · DOI
  31. Fruhbeis, C. et al. Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLOS Biol. 11, e1001604 (2013). · DOI · Paper page
  32. Fruhbeis, C., Frohlich, D., Kuo, W. P. & Kramer-Albers, E. M. Extracellular vesicles as mediators of neuron-glia communication. Front. Cell. Neurosci. 7, 182 (2013). · DOI
  33. Lafourcade, C., Ramirez, J. P., Luarte, A., Fernandez, A. & Wyneken, U. MiRNAs in astrocyte-derived exosomes as possible mediators of neuronal plasticity. J. Exp. Neurosci. 10, 1–9 (2016).
  34. Liu, Y. et al. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse. Sci. Rep. 5, 17543 (2015).
  35. Guitart, K. et al. Improvement of neuronal cell survival by astrocyte-derived exosomes under hypoxic and ischemic conditions depends on prion protein. Glia 64, 896–910 (2016). · DOI
  36. Luarte, A. et al. Astrocytes at the hub of the stress response: potential modulation of neurogenesis by miRNAs in astrocyte-derived exosomes. Stem Cells Int. 2017, 1719050 (2017). · DOI
  37. Zhang, Z. G. & Chopp, M. Exosomes in stroke pathogenesis and therapy. J. Clin. Invest. 126, 1190–1197 (2016). · DOI
  38. Ophelders, D. R. et al. Mesenchymal stromal cell-derived extracellular vesicles protect the fetal brain after hypoxia-ischemia. Stem Cells Transl Med. 5, 754–763 (2016). · DOI
  39. Doeppner, T. R. et al. Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression. Stem Cells Transl Med. 4, 1131–1143 (2015). · DOI
  40. Otero-Ortega, L. et al. White matter repair after extracellular vesicles administration in an experimental animal model of subcortical stroke. Sci. Rep. 7, 44433 (2017).
  41. Kim, D. K. et al. Chromatographically isolated CD63+CD81+ extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI. Proc. Natl Acad. Sci. USA 113, 170–175 (2015). · DOI
  42. Han, Y. et al. Multipotent mesenchymal stromal cell-derived exosomes improve functional recovery after experimental intracerebral hemorrhage in the rat. J. Neurosurg. https://doi.org/10.3171/2018.2.JNS171475 (2018). · DOI
  43. Otero-Ortega, L. et al. Exosomes promote restoration after an experimental animal model of intracerebral hemorrhage. J. Cereb. Blood Flow Metab. 38, 767–779 (2018). · DOI
  44. Williams, A. M. et al. Mesenchymal stem cell-derived exosomes provide neuroprotection and improve long-term neurologic outcomes in a swine model of traumatic brain injury and hemorrhagic shock. J. Neurotrauma https://doi.org/10.1089/neu.2018.5711 (2018). · DOI
  45. Buller, B. M. et al. Exosomes from rhesus monkey MSCs promote neuronal growth and myelination. Stroke 47 (Suppl. 1), A68 (2016).
  46. Orczykowski, M. E. et al. Cell based therapy enhances activation of ventral premotor cortex to improve recovery following primary motor cortex injury. Exp. Neurol. 305, 13–25 (2018). · DOI
  47. Moore, T. L. et al. Recovery from ischemia in the middle-aged brain: a nonhuman primate model. Neurobiol. Aging 33, 619.e9–619.e24 (2012). · DOI
  48. Bruhn, H. et al. Non-invasive differentiation of tumors with use of localized 1-H spectroscopy in vivo: initial experience in patients with cerebral tumors. Invest. Radiol. 25, 1047–1050 (1990). · DOI
  49. Marcus, M. E. & Leonard, J. N. FedExosomes: engineering therapeutic biological nanoparticles that truly deliver. Pharmaceuticals 6, 659–680 (2013). · DOI
  50. Zhang, Y. et al. Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2D and 3D conditions improves functional recovery in rats after traumatic brain injury. Neurochem. Int. 111, 69–81 (2016). · DOI
  51. Kordelas, L. et al. MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease. Leukemia 28, 970–973 (2014). · DOI
  52. Webb, R. L. et al. Human neural stem cell extracellular vesicles improve tissue and functional recovery in the murine thromboembolic stroke model. Transl Stroke Res. 9, 530–539 (2017). · DOI
  53. Webb, R. L. et al. Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke. Stroke 49, 1248–1256 (2018). · DOI
  54. Xiao, B. et al. Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia/reperfusion injury. Int. J. Mol. Med. 40, 1201–1209 (2017). · DOI
  55. Goyal, M., Hill, M. D., Saver, J. L. & Fisher, M. Challenges and opportunities of endovascular stroke therapy. Ann. Neurol. 79, 11–17 (2016). · DOI
  56. Fisher, M. & Saver, J. L. Future directions of acute ischaemic stroke therapy. Lancet Neurol. 14, 758–767 (2015). · DOI
  57. Neuhaus, A. A., Couch, Y., Hadley, G. & Buchan, A. M. Neuroprotection in stroke: the importance of collaboration and reproducibility. Brain 140, 2079–2092 (2017). · DOI
  58. Saver, J. L. et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA 316, 1279–1288 (2016). · DOI
  59. Jadhav, A. P. et al. Eligibility for endovascular trial enrollment in the 6- to 24-hour time window: analysis of a single comprehensive stroke center. Stroke 49, 1015–1017 (2018). · DOI
  60. Ganesh, A. & Goyal, M. Thrombectomy for acute ischemic stroke: recent insights and future directions. Curr. Neurol. Neurosci. Rep. 18, 59 (2018). · DOI
  61. Lapchak, P. A., Boitano, P. D., de Couto, G. & Marban, E. Intravenous xenogeneic human cardiosphere-derived cell extracellular vesicles (exosomes) improves behavioral function in small-clot embolized rabbits. Exp. Neurol. 307, 109–117 (2018). · DOI
  62. Billing, A. M. et al. Comprehensive transcriptomic and proteomic characterization of human mesenchymal stem cells reveals source specific cellular markers. Sci. Rep. 6, 21507 (2016). · DOI
  63. Walczak, P. et al. Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia. Stroke 39, 1569–1574 (2008). · DOI
  64. Herberts, C. A., Kwa, M. S. & Hermsen, H. P. Risk factors in the development of stem cell therapy. J. Transl Med. 9, 29 (2011). · DOI
  65. Wong, R. S. Mesenchymal stem cells: angels or demons? J. Biomed. Biotechnol. 2011, 459510 (2011).
  66. Krupinski, J., Kaluza, J., Kumar, P., Kumar, S. & Wang, J. M. Role of angiogenesis in patients with cerebral ischemic stroke. Stroke 25, 1794–1798 (1994). · DOI
  67. Jin, K. et al. Evidence for stroke-induced neurogenesis in the human brain. Proc. Natl Acad. Sci. USA 103, 13198–13202 (2006). · DOI
  68. Macas, J., Nern, C., Plate, K. H. & Momma, S. Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain. J. Neurosci. 26, 13114–13119 (2006). · DOI
  69. Minger, S. L. et al. Endogenous neurogenesis in the human brain following cerebral infarction. Regen. Med. 2, 69–74 (2007). · DOI
  70. Xin, H., Li, Y. & Chopp, M. Exosomes/miRNAs as mediating cell-based therapy of stroke. Front. Cell. Neurosci. 8, 377 (2014).
  71. Xiong, Y., Mahmood, A. & Chopp, M. Emerging potential of exosomes for treatment of traumatic brain injury. Neural Regen. Res. 12, 19–22 (2017). · DOI · Paper page
  72. Andras, I. E. & Toborek, M. Extracellular vesicles of the blood-brain barrier. Tissue Barriers 4, e1131804 (2016). · DOI
  73. Grange, C. et al. Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a model of acute kidney injury monitored by optical imaging. Int. J. Mol. Med. 33, 1055–1063 (2014). · DOI
  74. Di Rocco, G., Baldari, S. & Toietta, G. Towards therapeutic delivery of extracellular vesicles: strategies for in vivo tracking and biodistribution analysis. Stem Cells Int. 2016, 5029619 (2016). · DOI
  75. Betzer, O. et al. In vivo neuroimaging of exosomes using gold nanoparticles. ACS Nano 11, 10883–10893 (2017). · DOI
  76. Hwang, D. W. et al. Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using (99m)Tc-HMPAO. Sci. Rep. 5, 15636 (2015).
  77. Yuan, D. et al. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials 142, 1–12 (2017). · DOI · Paper page
  78. Zhang, Y. et al. Exosomes derived from mesenchymal stromal cells promote axonal growth of cortical neurons. Mol. Neurobiol. 54, 2659–2673 (2017). · DOI
  79. Tassew, N. G. et al. Exosomes mediate mobilization of autocrine Wnt10b to promote axonal regeneration in the injured CNS. Cell Rep. 20, 99–111 (2017). · DOI
  80. Haqqani, A. S. et al. Method for isolation and molecular characterization of extracellular microvesicles released from brain endothelial cells. Fluids Barriers CNS 10, 4 (2013). · DOI
  81. Pan, W. et al. Exosomes derived from ischemic cerebral endothelial cells and neural progenitor cells enhance neurogenesis and angiogenesis. Stroke 47 (Suppl. 1), AWMP39 (2016).
  82. Andras, I. E. et al. Extracellular vesicles of the blood-brain barrier: role in the HIV-1 associated amyloid beta pathology. Mol. Cell. Neurosci. 79, 12–22 (2017). · DOI
  83. Xin, H. et al. Secondary release of exosomes from astrocytes contributes to the increase in neural plasticity and improvement of functional recovery after stroke in rats treated with exosomes harvested from microRNA 133b-overexpressing multipotent mesenchymal stromal cells. Cell Transplant. 26, 243–257 (2017). · DOI
  84. Couch, Y. et al. Inflammatory stroke extracellular vesicles induce macrophage activation. Stroke 48, 2292–2296 (2017). · DOI
  85. Esenwa, C. C. & Elkind, M. S. Inflammatory risk factors, biomarkers and associated therapy in ischaemic stroke. Nat. Rev. Neurol. 12, 594–604 (2016). · DOI
  86. Drommelschmidt, K. et al. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury. Brain Behav. Immun. 60, 220–232 (2017). · DOI
  87. Cui, G. H. et al. Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. FASEB J. 32, 654–668 (2017).
  88. Chen, J. et al. MiR-126 affects brain-heart interaction after cerebral ischemic stroke. Transl Stroke Res. 8, 374–385 (2017). · DOI · Paper page
  89. Balusu, S. et al. Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO Mol. Med. 8, 1162–1183 (2016). · DOI
  90. Chopp, M. & Zhang, Z. G. Emerging potential of exosomes and noncoding microRNAs for the treatment of neurological injury/diseases. Expert Opin. Emerg. Drugs 20, 523–526 (2015). · DOI
  91. van Niel, G., D’Angelo, G. & Raposo, G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 19, 213–228 (2018). · DOI · Paper page
  92. Guduric-Fuchs, J. et al. Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types. BMC Genomics 13, 357 (2012). · DOI
  93. Melo, S. A. et al. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 26, 707–721 (2014). · DOI
  94. Collino, F. et al. AKI recovery induced by mesenchymal stromal cell-derived extracellular vesicles carrying microRNAs. J. Am. Soc. Nephrol. 26, 2349–2360 (2015). · DOI
  95. Zhang, R. L. et al. Cerebral endothelial derived exosomes abolish cognitive impairment induced by ablation of Dicer in adult neural stem cells. Stroke 48 (Suppl. 1), AWMP48 (2017).
  96. Mead, B. & Tomarev, S. Bone marrow-derived mesenchymal stem cells-derived exosomes promote survival of retinal ganglion cells through miRNA-dependent mechanisms. Stem Cells Transl Med. 6, 1273–1285 (2017). · DOI
  97. Katsuda, T., Oki, K. & Ochiya, T. Potential application of extracellular vesicles of human adipose tissue-derived mesenchymal stem cells in Alzheimer’s disease therapeutics. Methods Mol. Biol. 1212, 171–181 (2015). · DOI
  98. Xin, H. et al. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells 30, 1556–1564 (2012). · DOI
  99. Nam, J. W. et al. Global analyses of the effect of different cellular contexts on microRNA targeting. Mol. Cell 53, 1031–1043 (2014). · DOI
  100. He, Z. & Jin, Y. Intrinsic control of axon regeneration. Neuron 90, 437–451 (2016). · DOI
  101. Zhang, Y. et al. The microRNA-17-92 cluster enhances axonal outgrowth in embryonic cortical neurons. J. Neurosci. 33, 6885–6894 (2013). · DOI
  102. Jones, E. V. & Bouvier, D. S. Astrocyte-secreted matricellular proteins in CNS remodelling during development and disease. Neural Plast. 2014, 321209 (2014). · DOI
  103. Magill, S. T. et al. microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus. Proc. Natl Acad. Sci. USA 107, 20382–20387 (2010). · DOI · Paper page
  104. Dozio, V. & Sanchez, J. C. Characterisation of extracellular vesicle-subsets derived from brain endothelial cells and analysis of their protein cargo modulation after TNF exposure. J. Extracell. Vesicles 6, 1302705 (2017). · DOI
  105. Tkach, M. & Thery, C. Communication by extracellular vesicles: where we are and where we need to go. Cell 164, 1226–1232 (2016). · DOI · Paper page
  106. Alvarez-Erviti, L. et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29, 341–345 (2011). · DOI · Paper page
  107. Coimbra, J. R. M. et al. Highlights in BACE1 inhibitors for Alzheimer’s disease treatment. Front. Chem. 6, 178 (2018). · DOI
  108. Yang, J., Zhang, X., Chen, X., Wang, L. & Yang, G. Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia. Mol. Ther. Nucleic Acids 7, 278–287 (2017). · DOI · Paper page
  109. Gyorgy, B. et al. Rescue of hearing by gene delivery to inner-ear hair cells using exosome-associated AAV. Mol. Ther. 25, 379–391 (2017). · DOI · Paper page
  110. Tian, T. et al. Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials 150, 137–149 (2018). · DOI · Paper page
  111. Zhuang, X. et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol. Ther. 19, 1769–1779 (2011). · DOI · Paper page
  112. Kalani, A. et al. Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury. Int. J. Biochem. Cell Biol. 79, 360–369 (2016). · DOI
  113. Xin, H. et al. MicroRNA cluster miR-17-92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats. Stroke 48, 747–753 (2017). · DOI
  114. Shen, H. et al. Role of exosomes derived from miR-133b modified MSCs in an experimental rat model of intracerebral hemorrhage. J. Mol. Neurosci. 64, 421–430 (2018). · DOI
  115. Sterzenbach, U. et al. Engineered exosomes as vehicles for biologically active proteins. Mol. Ther. 25, 1269–1278 (2017). · DOI
  116. Long, Q. et al. Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. Proc. Natl Acad. Sci. USA 114, E3536–E3545 (2017). · DOI
  117. Haney, M. J. et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J. Control. Release 207, 18–30 (2015). · DOI · Paper page
  118. Pachler, K. et al. A Good Manufacturing Practice-grade standard protocol for exclusively human mesenchymal stromal cell-derived extracellular vesicles. Cytotherapy 19, 458–472 (2017). · DOI
  119. Gimona, M., Pachler, K., Laner-Plamberger, S., Schallmoser, K. & Rohde, E. Manufacturing of human extracellular vesicle-based therapeutics for clinical use. Int. J. Mol. Sci. 18, E1190 (2017). · DOI
  120. Frank, J. et al. Extracellular vesicles protect glucuronidase model enzymes during freeze-drying. Sci. Rep. 8, 12377 (2018).
  121. Pachler, K. et al. An in vitro potency assay for monitoring the immunomodulatory potential of stromal cell-derived extracellular vesicles. Int. J. Mol. Sci. 18, E1413 (2017). · DOI
  122. Reiner, A. T. et al. Concise review: developing best-practice models for the therapeutic use of extracellular vesicles. Stem Cells Transl Med. 6, 1730–1739 (2017). · DOI
  123. Anderson, J. D. et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappaB signaling. Stem Cells 34, 601–613 (2016). · DOI

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Metadata

Authors
Zhang, Z. G., Buller, B., & Chopp, M.
Venue
Nature Reviews Neurology
Publisher
Springer Science and Business Media LLC
Published
2019-01-30
Volume
15
Issue
4
Pages
193-203
ISSN
  • 1759-4758
  • 1759-4766
DOI
10.1038/s41582-018-0126-4
Cited by
503
References
12
Language
en
Licence
www.springer.com/tdm (tdm)

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