Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury
Open accessAbstract
OBJECT: Transplanted multipotent mesenchymal stromal cells (MSCs) improve functional recovery in rats after traumatic brain injury (TBI). In this study the authors tested a novel hypothesis that systemic administration of cell-free exosomes generated from MSCs promotes functional recovery and neurovascular remodeling in rats after TBI. METHODS: Two groups of 8 Wistar rats were subjected to TBI, followed 24 hours later by tail vein injection of 100 μg protein of exosomes derived from MSCs or an equal volume of vehicle (phosphate-buffered saline). A third group of 8 rats was used as sham-injured, sham-treated controls. To evaluate cognitive and sensorimotor functional recovery, the modified Morris water maze, modified Neurological Severity Score, and foot-fault tests were performed. Animals were killed at 35 days after TBI. Histopathological and immunohistochemical analyses were performed for measurements of lesion volume, neurovascular remodeling (angiogenesis and neurogenesis), and neuroinflammation. RESULTS: Compared with the saline-treated group, exosome-treated rats with TBI showed significant improvement in spatial learning at 34-35 days as measured by the modified Morris water maze test (p < 0.05), and sensorimotor functional recovery (i.e., reduced neurological deficits and foot-fault frequency) was observed at 14-35 days postinjury (p < 0.05). Exosome treatment significantly increased the number of newly generated endothelial cells in the lesion boundary zone and dentate gyrus and significantly increased the number of newly formed immature and mature neurons in the dentate gyrus as well as reducing neuroinflammation. CONCLUSIONS: The authors demonstrate for the first time that MSC-generated exosomes effectively improve functional recovery, at least in part, by promoting endogenous angiogenesis and neurogenesis and by reducing inflammation in rats after TBI. Thus, MSC-generated exosomes may provide a novel cell-free therapy for TBI and possibly for other neurological diseases.
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Exosomes can cross the blood-brain barrier and transport specific drugs to neural cells, significantly retaining side effects including toxicity.
“For instance, exosomes can cross the blood–brain barrier (BBB) and transport specific drugs to the neural cell [39], significantly retaining side effects including toxicity.”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [39]
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Cites
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Place navigation impaired in rats with hippocampal lesions
Morris, R. G. M., Garrud, P., Rawlins, J. N. P., & O'Keefe, J. (1982) · Nature · doi:10.1038/297681a0 · Cited by 6,340 · see citing works
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930 · see citing works
Mechanisms and Functional Implications of Adult Neurogenesis
Zhao, C., Deng, W., & Gage, F. H. (2008) · Cell · doi:10.1016/j.cell.2008.01.033 · Cited by 3,007 · see citing works
Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles
György, B., Szabó, T. G., Pásztói, M., Pál, Z., Misják, P., Aradi, B., László, V., Pállinger, É., Pap, E., Kittel, Á., et al. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0689-3 · Cited by 2,075 · see citing works
Vlassov, A. V., Magdaleno, S. M., Setterquist, R. A., & Conrad, R. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2012.03.017 · Cited by 1,936 · see citing works
Classification, Functions, and Clinical Relevance of Extracellular Vesicles
van der Pol, E., Böing, A. N., Harrison, P., Sturk, A., & Nieuwland, R. (2012) · Pharmacological Reviews · doi:10.1124/pr.112.005983 · Cited by 1,756 · see citing works
Shedding microvesicles: artefacts no more
Cocucci, E., Racchetti, G., & Meldolesi, J. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.11.003 · Cited by 1,742 · see citing works
A Semiautomated Method for Measuring Brain Infarct Volume
Swanson, R., Morton, M. T., Tsao-Wu, G., Savalos, R. A., Davidson, C., & Sharp, F. (1990) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1038/jcbfm.1990.47 · Cited by 1,727 · see citing works
Animal models of traumatic brain injury
Xiong, Y., Mahmood, A., & Chopp, M. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3407 · Cited by 1,413 · see citing works
Self-citationChen, J., Sanberg, P. R., Li, Y., Wang, L., Lü, M., Willing, A. E., Sanchez‐Ramos, J., & Chopp, M. (2001) · Stroke · doi:10.1161/hs1101.098367 · Cited by 1,347 · see citing works
Self-citationTauro, B. J., Greening, D. W., Mathias, R. A., Ji, H. L., Mathivanan, S., Scott, A. M., & Simpson, R. J. (2012) · Methods · doi:10.1016/j.ymeth.2012.01.002 · Cited by 1,177 · see citing works
A controlled cortical impact model of traumatic brain injury in the rat
Edward Dixon, C., Clifton, G. L., Lighthall, J. W., Yaghmai, A. A., & Hayes, R. L. (1991) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(91)90104-8 · Cited by 1,141 · see citing works
Exosome: from internal vesicle of the multivesicular body to intercellular signaling device
Denzer, K., Kleijmeer, M. J., Heijnen, H. F. G., Stoorvogel, W., & Geuze, H. J. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.19.3365 · Cited by 1,067 · see citing works
Xin, H., Li, Y., Cui, Y., Yang, J. J., Zhang, Z. G., & Chopp, M. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.152 · Cited by 985 · see citing works
Self-citationMicrovesicles: mediators of extracellular communication during cancer progression
Muralidharan-Chari, V., Clancy, J. W., Sedgwick, A., & D’Souza‐Schorey, C. (2010) · Journal of Cell Science · doi:10.1242/jcs.064386 · Cited by 951 · see citing works
Paracrine Mechanisms of Mesenchymal Stem Cell-Based Therapy: Current Status and Perspectives
Liang, X., Ding, Y., Zhang, Y., Tse, H.-F., & Lian, Q. (2014) · Cell Transplantation · doi:10.3727/096368913x667709 · Cited by 909 · see citing works
Self-citationXin, H., Li, Y., Buller, B., Katakowski, M., Zhang, Y., Wang, X., Shang, X., Zhang, Z. G., & Chopp, M. (2012) · Stem Cells · doi:10.1002/stem.1129 · Cited by 897 · see citing works
Self-citationA Neurovascular Niche for Neurogenesis after Stroke
Ohab, J. J., Fleming, S., Blesch, A., & Carmichael, S. T. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4323-06.2006 · Cited by 878 · see citing works
The Biogenesis and Functions of Exosomes
Stoorvogel, W., Kleijmeer, M. J., Geuze, H. J., & Raposo, G. (2002) · Traffic · doi:10.1034/j.1600-0854.2002.30502.x · Cited by 848 · see citing works
Exosomes Derived from Mesenchymal Stem Cells
Yu, B., Zhang, X., & Li, X. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15034142 · Cited by 788 · see citing works
Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth
Katakowski, M., Buller, B., Zheng, X., Lü, Y., Rogers, T., Osobamiro, O. O., Shu, W., Jiang, F., & Chopp, M. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.02.019 · Cited by 748 · see citing works
Self-citationXin, H., Li, Y., Liu, Z., Wang, X., Shang, X., Cui, Y., Zhang, Z. G., & Chopp, M. (2013) · Stem Cells · doi:10.1002/stem.1409 · Cited by 724 · see citing works
Self-citationThe Role of Markers of Inflammation in Traumatic Brain Injury
Woodcock, T. M., & Morganti-Kossmann, M. C. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00018 · Cited by 719 · see citing works
Treatment of neural injury with marrow stromal cells
Chopp, M., & Li, Y. (2002) · The Lancet Neurology · doi:10.1016/s1474-4422(02)00040-6 · Cited by 624 · see citing works
Self-citationA new penumbra: transitioning from injury into repair after stroke
Lo, E. H. (2008) · Nature Medicine · doi:10.1038/nm1735 · Cited by 611 · see citing works
Gruenberg, J. E., Griffiths, G. W., & Howell, K. E. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.108.4.1301 · Cited by 586 · see citing works
Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease
Lai, R. C., Chen, T. S., & Lim, S. K. (2011) · Regenerative Medicine · doi:10.2217/rme.11.35 · Cited by 553 · see citing works
Exosome-dependent Trafficking of HSP70
Lancaster, G. I., & Febbraio, M. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502017200 · Cited by 547 · see citing works
Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum
Jin, K., Sun, Y., Xie, L., Peel, A. L., Mao, X. O., Parmentier‐Batteur, S., & Greenberg, D. A. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(03)00159-3 · Cited by 515 · see citing works
Mesenchymal stem cells for the treatment of neurodegenerative disease
Joyce, N. C., Annett, G., Wirthlin, L., Olson, S. D., Bauer, G., & Nolta, J. A. (2010) · Regenerative Medicine · doi:10.2217/rme.10.72 · Cited by 504 · see citing works
Deng, W., Saxe, M. D., Gallina, I. S., & Gage, F. H. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3362-09.2009 · Cited by 493 · see citing works
Cvjetkovic, A., Lötvall, J. O., & Lässer, C. (2014) · Journal of Extracellular Vesicles · doi:10.3402/jev.v3.23111 · Cited by 489 · see citing works
Mahmood, A., Lu, D., Lü, M., & Chopp, M. (2003) · Neurosurgery · doi:10.1227/01.neu.0000079333.61863.aa · Cited by 478 · see citing works
Self-citationPant, S., Hilton, H., & Burczynski, M. E. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.12.037 · Cited by 470 · see citing works
Atorvastatin Induction of VEGF and BDNF Promotes Brain Plasticity after Stroke in Mice
Chen, J., Zhang, C., Jiang, H., Li, Y., Zhang, L., Robin, A. M., Katakowski, M., Lü, M., & Chopp, M. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600034 · Cited by 451 · see citing works
Self-citationTreatment of stroke in rat with intracarotid administration of marrow stromal cells
Li, Y., Chen, J., Wang, L., Lü, M., & Chopp, M. (2001) · Neurology · doi:10.1212/wnl.56.12.1666 · Cited by 431 · see citing works
Self-citationForebrain neurogenesis after focal Ischemic and traumatic brain injury
Kernie, S. G., & Parent, J. M. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.11.002 · Cited by 426 · see citing works
The therapeutic potential of mesenchymal stem cell‐derived extracellular vesicles
Katsuda, T., Kosaka, N., Takeshita, F., & Ochiya, T. (2013) · PROTEOMICS · doi:10.1002/pmic.201200373 · Cited by 425 · see citing works
Exosome Isolation for Proteomic Analyses and RNA Profiling
Taylor, D. D., Zacharias, W., & Gerçel-Taylor, Ç. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-068-3_15 · Cited by 395 · see citing works
Zhang, R., Liu, Y., Yan, K., Chen, L., Chen, X.-R., Li, P., Chen, F.-F., & Jiang, X.-D. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-106 · Cited by 377 · see citing works
Mahmood, A., Lu, D., & Chopp, M. (2004) · Journal of Neurotrauma · doi:10.1089/089771504772695922 · Cited by 349 · see citing works
Self-citationLu, D., Mahmood, A., Wang, L., Li, Y., Lü, M., & Chopp, M. (2001) · Neuroreport · doi:10.1097/00001756-200103050-00025 · Cited by 334 · see citing works
Self-citationAngiogenesis, neurogenesis and brain recovery of function following injury.
Xiong, Y., Mahmood, A., & Chopp, M. (2010) · PubMed · Cited by 297 · see citing works
Self-citationExtracellular vesicles: structure, function, and potential clinical uses in renal diseases
Borges, F. T., Reis, L. A., & Schor, N. (2013) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20132964 · Cited by 294 · see citing works
Chen, X., Katakowski, M., Li, Y., Lu, D., Wang, L., Zhang, L., Chen, J., Xu, Y., Gautam, S. C., Mahmood, A., et al. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10334 · Cited by 293 · see citing works
Self-citationArai, K., Jin, G., Navaratna, D., & Lo, E. H. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07176.x · Cited by 286 · see citing works
Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases
Masyuk, A. I., Masyuk, T. V., & LaRusso, N. F. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.028 · Cited by 283 · see citing works
Lu, D., Mahmood, A., Qu, C., Goussev, A. V., Schallert, T. J., & Chopp, M. (2005) · Journal of Neurotrauma · doi:10.1089/neu.2005.22.1011 · Cited by 265 · see citing works
Self-citationHeterogeneity of mesenchymal stromal cell preparations
Ho, A. D., Wagner, W., & Franke, W. W. (2008) · Cytotherapy · doi:10.1080/14653240802217011 · Cited by 265 · see citing works
Marrow stromal cell transplantation in stroke and traumatic brain injury
Li, Y., & Chopp, M. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2008.03.096 · Cited by 222 · see citing works
Self-citationMonocyte Exosomes Stimulate the Osteogenic Gene Expression of Mesenchymal Stem Cells
Ekström, K. M., Omar, O., Granéli, C., Wang, X., Vazirisani, F., & Thomsen, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075227 · Cited by 219 · see citing works
Intraarterial Administration of Marrow Stromal Cells in a Rat Model of Traumatic Brain Injury
Lu, D., Li, Y., Wang, L., Chen, J., Mahmood, A., & Chopp, M. (2001) · Journal of Neurotrauma · doi:10.1089/089771501316919175 · Cited by 216 · see citing works
Self-citationKleindienst, A., McGinn, M. J., Harvey, H. B., Colello, R. J., Hamm, R. J., & Bullock, M. R. (2005) · Journal of Neurotrauma · doi:10.1089/neu.2005.22.645 · Cited by 207 · see citing works
Sun, D., McGinn, M. J., Zhou, Z., Harvey, H. B., Bullock, M. R., & Colello, R. J. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2006.11.005 · Cited by 182 · see citing works
Hailer, N. P. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.12.001 · Cited by 181 · see citing works
Mahmood, A., Lu, D., Wang, L., & Chopp, M. (2002) · Journal of Neurotrauma · doi:10.1089/089771502762300265 · Cited by 181 · see citing works
Self-citationUncovering the secretes of mesenchymal stem cells
Lavoie, J. R., & Rosu‐Myles, M. (2013) · Biochimie · doi:10.1016/j.biochi.2013.06.017 · Cited by 176 · see citing works
Neurogenesis in Adult Human Brain after Traumatic Brain Injury
Zheng, W., Zhuge, Q., Zhong, M., Chen, G., Shao, B., Wang, H., Mao, X., Xie, L., & Jin, K. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2010.1579 · Cited by 173 · see citing works
Neurorestorative treatment of stroke: Cell and pharmacological approaches
Chen, J., & Chopp, M. (2006) · NeuroRx · doi:10.1016/j.nurx.2006.07.007 · Cited by 169 · see citing works
Self-citationNeurogenesis After Traumatic Brain Injury
Richardson, R. M., Sun, D., & Bullock, M. R. (2007) · Neurosurgery Clinics of North America · doi:10.1016/j.nec.2006.10.007 · Cited by 164 · see citing works
Autologous Bone Marrow Mononuclear Cell Therapy for Severe Traumatic Brain Injury in Children
Cox, C., Baumgartner, J., Harting, M., Worth, L., Walker, P. A., Shah, S. K., Ewing-Cobbs, L., Hasan, K., Day, M., Lee, D. A., et al. (2011) · Neurosurgery · doi:10.1227/neu.0b013e318207734c · Cited by 163 · see citing works
A review of neuroprotection pharmacology and therapies in patients with acute traumatic brain injury
McConeghy, K. W., Hatton, J., Hughes, L., & Cook, A. M. (2012) · CNS Drugs · doi:10.2165/11634020-000000000-00000 · Cited by 158 · see citing works
Zhang, Z.-X., Guan, L., Zhang, K., Zhang, Q., & Dai, L. (2008) · Cytotherapy · doi:10.1080/14653240701883061 · Cited by 151 · see citing works
Subventricular Zone Neuroblasts Emigrate Toward Cortical Lesions
Sundholm‐Peters, N. L., Yang, H. K. C., Goings, G. E., Walker, A. S., & Szele, F. G. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000190066.13312.8f · Cited by 148 · see citing works
Blaiss, C. A., Yu, T., Zhang, G., Chen, J., Dimchev, G. A., Parada, L. F., Powell, C. M., & Kernie, S. G. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5265-10.2011 · Cited by 148 · see citing works
Baskin, Y. K., Dietrich, W. D., & Green, E. J. (2003) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(03)00212-7 · Cited by 147 · see citing works
MicroRNA transport: A new way in cell communication
Xu, L., Yang, B., & Ai, J. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24344 · Cited by 138 · see citing works
Li, B., Mahmood, A., Lu, D., Wu, H., Xiong, Y., Qu, C., & Chopp, M. (2009) · Neurosurgery · doi:10.1227/01.neu.0000346272.76537.dc · Cited by 133 · see citing works
Self-citationLu, D., Mahmood, A., Qu, C., Hong, X., Kaplan, D. L., & Chopp, M. (2007) · Neurosurgery · doi:10.1227/01.neu.0000290908.38438.b2 · Cited by 131 · see citing works
Self-citationMesenchymal Stem Cell Exosome Ameliorates Reperfusion Injury Through Proteomic Complementation
Lai, R. C., Yeo, R. W. Y., Tan, K. H., & Lim, S. K. (2013) · Regenerative Medicine · doi:10.2217/rme.13.4 · Cited by 129 · see citing works
Concise Review: MicroRNA Expression in Multipotent Mesenchymal Stromal Cells
Lakshmipathy, U., & Hart, R. P. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0625 · Cited by 126 · see citing works
Microvesicles and intercellular communication in the context of parasitism
Barteneva, N. S., Maltsev, N., & Vorobjev, I. A. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00049 · Cited by 120 · see citing works
Li, L., Jiang, Q., Zhang, L., Ding, G., Zhang, Z. G., Li, Q., Ewing, J. R., Lü, M., Panda, S., Ledbetter, K. A., et al. (2007) · Brain Research · doi:10.1016/j.brainres.2006.10.098 · Cited by 119 · see citing works
Self-citationCell-derived microvesicles and cancer.
van Doormaal, F. F., Kleinjan, A., Nisio, M. D., Buller, H. R., & Nieuwland, R. (2009) · PubMed · Cited by 115 · see citing works
Plasticity and remodeling of brain
Chopp, M., Li, Y., & Zhang, J. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.06.013 · Cited by 115 · see citing works
Self-citationXiong, Y., Mahmood, A., Meng, Y., Zhang, Y., Qu, C., Schallert, T. J., & Chopp, M. (2009) · Journal of neurosurgery · doi:10.3171/2009.9.jns09844 · Cited by 111 · see citing works
Self-citationLu, D., Mahmood, A., Goussev, A. V., Schallert, T. J., Qu, C., Zhang, Z. G., Li, Y., Lü, M., & Chopp, M. (2004) · Journal of neurosurgery · doi:10.3171/jns.2004.101.5.0813 · Cited by 107 · see citing works
Self-citationTsai, M., Tsai, S.-K., Hu, B.-R., Liou, D.-Y., Huang, S., Huang, W., Cheng, H., Cheng, H., & Huang, S.-S. (2014) · Journal of Biomedical Science · doi:10.1186/1423-0127-21-5 · Cited by 106 · see citing works
Schwab, J. M., Beschorner, R., Nguyen, T., et al. (2001) · Journal of Neurotrauma · doi:10.1089/089771501750170930 · Cited by 97 · see citing works
Nishibe, M., Barbay, S., Guggenmos, D. J., & Nudo, R. J. (2010) · Journal of Neurotrauma · doi:10.1089/neu.2010.1456 · Cited by 94 · see citing works
Mahmood, A., Lu, D., Qu, C., Goussev, A. V., & Chopp, M. (2007) · Neurosurgery · doi:10.1227/01.neu.0000255346.25959.99 · Cited by 87 · see citing works
Self-citationMorgan, R., Kreipke, C. W., Roberts, G. G., Bagchi, M., & Rafols, J. A. (2007) · Neurological Research · doi:10.1179/016164107x204693 · Cited by 80 · see citing works
Choi, S. H., Woodlee, M. T., Hong, J. J., & Schallert, T. J. (2006) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2006.03.002 · Cited by 79 · see citing works
Astrocytes and Microglia: Responses to Neuropathological Conditions
Singh, S., Swarnkar, S., Goswami, P., & Nath, C. (2011) · International Journal of Neuroscience · doi:10.3109/00207454.2011.598981 · Cited by 77 · see citing works
Nichols, J. E., Niles, J. A., DeWitt, D. S., et al. (2013) · Stem Cell Research & Therapy · doi:10.1186/scrt151 · Cited by 76 · see citing works
Treatment of traumatic brain injury with thymosin β4 in rats
Xiong, Y., Mahmood, A., Meng, Y., Zhang, Y., Zhang, Z. G., Morris, D. C., & Chopp, M. (2010) · Journal of neurosurgery · doi:10.3171/2010.4.jns10118 · Cited by 75 · see citing works
Self-citationInosine promotes recovery of skilled motor function in a model of focal brain injury
Smith, J. M., Lunga, P., Story, D., Harris, N. G., Belle, J. E. L., James, M. F., Pickard, J. D., & Fawcett, J. W. (2006) · Brain · doi:10.1093/brain/awl393 · Cited by 72 · see citing works
Dynamics of Intracellular Granules with CD63-GFP in Rat Basophilic Leukemia Cells
Amano, T., Furuno, T., Hirashima, N., et al. (2001) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a002914 · Cited by 69 · see citing works
Xiong, Y., Mahmood, A., Zhang, Y.-L., Meng, Y.-L., Zhang, Z.-G., Qu, C., Sager, T., & Chopp, M. (2010) · Journal of Neurosurgery · doi:10.3171/2010.10.jns10925 · Cited by 67 · see citing works
Self-citationMeng, Y., Xiong, Y., Mahmood, A., Zhang, Y., Qu, C., & Chopp, M. (2011) · Journal of neurosurgery · doi:10.3171/2011.3.jns101721 · Cited by 66 · see citing works
Self-citationXiong, Y., Zhang, Y., Mahmood, A., Meng, Y., Qu, C., & Chopp, M. (2011) · Translational Stroke Research · doi:10.1007/s12975-011-0120-2 · Cited by 66 · see citing works
Self-citationExosomes: A New Weapon to Treat the Central Nervous System
Braccioli, L., van Velthoven, C. T. J., & Heijnen, C. J. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8504-9 · Cited by 65 · see citing works
Walker, P. A., Shah, S. K., Jiménez, F., Aroom, K., Harting, M. T., & Cox, C. S. (2012) · Surgery · doi:10.1016/j.surg.2012.06.006 · Cited by 58 · see citing works
Zhang, Y., Chopp, M., Meng, Y., Zhang, Z. G., Doppler, E., Mahmood, A., & Xiong, Y. (2013) · Journal of neurosurgery · doi:10.3171/2013.3.jns122061 · Cited by 52 · see citing works
Self-citationLin, B., Ginsberg, M. D., Zhao, W., Alonso, O. F., Belayev, L., & Busto, R. (2001) · Journal of Neurotrauma · doi:10.1089/089771501750170958 · Cited by 51 · see citing works
The cardiovascular exosome: Current perspectives and potential
Cosme, J., Liu, P. P., & Gramolini, A. O. (2013) · PROTEOMICS · doi:10.1002/pmic.201200441 · Cited by 49 · see citing works
The therapeutic potential of adult neural stem cells.
Taupin, P. (2006) · PubMed · Cited by 48 · see citing works
Zhang, Y., Chopp, M., Mahmood, A., Meng, Y., Qu, C., & Xiong, Y. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.02.015 · Cited by 45 · see citing works
Self-citationMahmood, A., Goussev, A. V., Lu, D., Qu, C., Xiong, Y., Kazmi, H., & Chopp, M. (2008) · Journal of Neurotrauma · doi:10.1089/neu.2007.0495 · Cited by 45 · see citing works
Self-citationImmature and mature neurons coexist among glial scars after rat traumatic brain injury
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- Authors
- Zhang, Y., Chopp, M., Meng, Y., Katakowski, M., Xin, H., Mahmood, A., & Xiong, Y.
- Affiliations
- Departments of Neurosurgery and
- Oakland University (US)
- Henry Ford Hospital (US)
- Venue
- Journal of neurosurgery
- Published
- 2015-04
- Volume
- 122
- Issue
- 4
- Pages
- 856-867
- ISSN
- 0022-3085 (ISSN-L)
- 1933-0693
- PMC
- PMC4382456
- OpenAlex
- W2168120562
- Cited by
- 737
- References
- 107
- Citations by year
- 2026: 32 · 2025: 61 · 2024: 71 · 2023: 64 · 2022: 84 · 2021: 92 · 2020: 85 · 2019: 82 · 2018: 56 · 2017: 53 · 2016: 39 · 2015: 17 · 2014: 1
- FWCI
- 23.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of neurosurgery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS081189)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- exosomes, mesenchymal stem cells, traumatic brain injury, cell-free therapy, functional recovery, angiogenesis, neurogenesis, neuroinflammation, spatial learning, sensorimotor recovery, dentate gyrus
- MeSH terms
- Doublecortin Protein, Animals, Blood Vessels, Brain Injuries, Cell Count, Cognition, Injections, Intravenous, Male, Neuronal Plasticity, Sensation, Rats, Wistar, Maze Learning, Recovery of Function, Pluripotent Stem Cells, Mesenchymal Stem Cell Transplantation, Rats, Exosomes, Mesenchymal Stem Cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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