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Bone Marrow-Derived Cells that Populate the Adult Mouse Brain Preserve Their Hematopoietic Identity
Open accessAbstract
Cytogenesis in the adult brain can result from the recruitment of circulating precursors, but the proposal that some such cells transdifferentiate into neural elements is controversial. We have reinvestigated this issue by following the phenotypic fate of bone marrow cells expressing the green fluorescent protein transplanted into the systemic circulation of irradiated mice. Thousands of donor-derived cells were detected throughout brains of recipients killed 1-12 months after transplantation, but none displayed neuronal, macroglial, or endothelial characteristics, even after injury. Among those that crossed the endothelium of the cerebral cortex, >99.7% were identified as perivascular macrophages. Newly formed parenchymal microglia were found in significant numbers only in the cerebellum and at injury sites. Therefore, bone marrow does supply the mature brain with new specialized cells; however, mesenchymal precursors neither adopt neural phenotypes nor contribute to cerebral vascular remodeling. This continuous traffic of macrophages across the blood-brain barrier provides a vehicle to introduce therapeutic genes into the nervous system.
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“Residing in the intracerebral perivascular space, delimited by the glia limitans and the vascular basement membrane (Virchow-Robin space), PVMs are closely apposed to the outer vessel wall and originate from hematopoietic precursors (18,20,21).”
From Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension (2016) · cites this paper as [21]
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Cites
Gage, F. H. (2000) · Science · doi:10.1126/science.287.5457.1433 · Cited by 4,786
Estimation of nuclear population from microtome sections
Abercrombie, M. (1946) · The Anatomical Record · doi:10.1002/ar.1090940210 · Cited by 4,363
Kocher, A. A., Schuster, M., Szabolcs, M., Takuma, S., Burkhoff, D., Wang, J., Homma, S., Edwards, N. M., & Itescu, S. (2001) · Nature Medicine · doi:10.1038/86498 · Cited by 2,524
Takahashi, T., Kalka, C., Masuda, H., Chen, D., Silver, M., Kearney, M., Magner, M., Isner, J. M., & Asahara, T. (1999) · Nature Medicine · doi:10.1038/7434 · Cited by 2,421
Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion
Terada, N., Hamazaki, T., Oka, M., Hoki, M., Mastalerz, D. M., Nakano, Y., Meyer, E. M., Morel, L. M., Petersen, B. E., & Scott, E. W. (2002) · Nature · doi:10.1038/nature730 · Cited by 2,000
Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization
Kalka, C., Masuda, H., Takahashi, T., Kalka-Moll, W. M., Silver, M., Kearney, M., Li, T., Isner, J. M., & Asahara, T. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3422 · Cited by 1,961
Weissman, I. L. (2000) · Cell · doi:10.1016/s0092-8674(00)81692-x · Cited by 1,827
Turning Blood into Brain: Cells Bearing Neuronal Antigens Generated in Vivo from Bone Marrow
Mezey, É., Chandross, K. J., Harta, G., Maki, R. A., & McKercher, S. R. (2000) · Science · doi:10.1126/science.290.5497.1779 · Cited by 1,814
From Marrow to Brain: Expression of Neuronal Phenotypes in Adult Mice
Brazelton, T. R., Rossi, F. M. V., Keshet, G. I., & Blau, H. M. (2000) · Science · doi:10.1126/science.290.5497.1775 · Cited by 1,666
Kopen, G. C., Prockop, D. J., & Phinney, D. G. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.19.10711 · Cited by 1,643
Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus
Cameron, H. A., & Mckay, R. D. G. (2001) · Journal of Comparative Neurology · doi:10.1002/cne.1040 · Cited by 1,585
Adult Bone Marrow Stromal Cells Differentiate into Neural Cells in Vitro
Sanchez‐Ramos, J., Song, S., Cardozo‐Pelaez, F., Hazzi, C., Stedeford, T. J., Willing, A. E., Freeman, T. B., Saporta, S., Janssen, W. E., Patel, N. A., et al. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7389 · Cited by 1,568
Changing potency by spontaneous fusion
Ying, Q.-L., Nichols, J., Evans, E. P., & Smith, A. G. (2002) · Nature · doi:10.1038/nature729 · Cited by 1,494
Microglia-specific localisation of a novel calcium binding protein, Iba1
Ito, D., Imai, Y., Ohsawa, K., Nakajima, K., Fukuuchi, Y., & Kohsaka, S. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00040-0 · Cited by 1,476
Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem Cells
Wagers, A. J., Sherwood, R. I., Christensen, J. L., & Weissman, I. L. (2002) · Science · doi:10.1126/science.1074807 · Cited by 1,460
Streit, W. J., Walter, S. A., & Pennell, N. A. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00069-0 · Cited by 1,096
The Evolving Concept of a Stem Cell
Blau, H. M., Brazelton, T. R., & Weimann, J. M. (2001) · Cell · doi:10.1016/s0092-8674(01)00409-3 · Cited by 1,044
Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice
Eglitis, M. A., & Mezey, É. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4080 · Cited by 1,015
Schmued, L. C., Albertson, C., & Slikker, W. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01387-x · Cited by 995
Abnormalities in Pericytes on Blood Vessels and Endothelial Sprouts in Tumors
Morikawa, S., Bałuk, P., Kaidoh, T., Haskell, A., Jain, R. K., & McDonald, D. M. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64920-6 · Cited by 987
Physiological Migration of Hematopoietic Stem and Progenitor Cells
Wright, D. E., Wagers, A. J., Gulati, A. P., Johnson, F. L., & Weissman, I. L. (2001) · Science · doi:10.1126/science.1064081 · Cited by 933
Zhao, L.-R., Duan, W.-M., Reyes, M., Keene, C. D., Verfaillie, C. M., & Low, W. C. (2002) · Experimental Neurology · doi:10.1006/exnr.2001.7853 · Cited by 828
Fuchs, E. V., & Segre, J. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81691-8 · Cited by 762
Turnover of resident microglia in the normal adult mouse brain
Lawson, L. J., Perry, V. H., & Gordon, S. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90500-2 · Cited by 709
The role of microglia and macrophages in the pathophysiology of the CNS
Stollg, G., & Jander, S. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00083-5 · Cited by 683
Priller, J., Flügel, A., Wehner, T., Boentert, M., Haas, C. A., Prinz, M., Fernández-Klett, F., Prass, K., Bechmann, I., de Boer, B. A., et al. (2001) · Nature Medicine · doi:10.1038/nm1201-1356 · Cited by 637
Transplanted bone marrow generates new neurons in human brains
Mezey, É., Key, S., Vogelsang, G. B., Szalayova, I., Lange, G. D., & Crain, B. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0336479100 · Cited by 565
Crane, G. M., Mosher, J. T., Bixby, S., Joseph, N. M., Iwashita, T., & Morrison, S. J. (2002) · Neuron · doi:10.1016/s0896-6273(02)00827-9 · Cited by 543
Can stem cells cross lineage boundaries?
Anderson, D. J., Gage, F. H., & Weissman, I. L. (2001) · Nature Medicine · doi:10.1038/86439 · Cited by 489
Augmentation of Postnatal Neovascularization With Autologous Bone Marrow Transplantation
Shintani, S., Murohara, T., Ikeda, H., Ueno, T., Sasaki, K., Duan, J., & Imaizumi, T. (2001) · Circulation · doi:10.1161/01.cir.103.6.897 · Cited by 457
Zhang, Z. G., Zhang, L., Jiang, Q., & Chopp, M. (2002) · Circulation Research · doi:10.1161/hh0302.104460 · Cited by 453
Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization
Kalka, C. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.070046397 · Cited by 451
Failure of Bone Marrow Cells to Transdifferentiate into Neural Cells in Vivo
Castro, R. F., Jackson, K. A., Goodell, M. A., Robertson, C. S., Liu, H., & Shine, H. D. (2002) · Science · doi:10.1126/science.297.5585.1299 · Cited by 438
Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains
Weimann, J. M., Charlton, C. A., Brazelton, T. R., Hackman, R. C., & Blau, H. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337659100 · Cited by 429
Remyelination of the Rat Spinal Cord by Transplantation of Identified Bone Marrow Stromal Cells
Akiyama, Y., Radtke, C., & Kocsis, J. D. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-15-06623.2002 · Cited by 372
Cellular forms and functions of brain microglia
Davis, E. J., Foster, T. D., & Thomas, W. E. (1994) · Brain Research Bulletin · doi:10.1016/0361-9230(94)90189-9 · Cited by 359
Brain macrophages: on the role of pericytes and perivascular cells
Thomas, W. E. (1999) · Brain Research Reviews · doi:10.1016/s0165-0173(99)00024-7 · Cited by 306
Kohyama, J., Abe, H., Shimazaki, T., Koizumi, A., Nakashima, K., Gojo, S., Taga, T., Okano, H., Hata, J.-I., & Umezawa, A. (2001) · Differentiation · doi:10.1046/j.1432-0436.2001.680411.x · Cited by 295
Differentiation of Mesencephalic Progenitor Cells into Dopaminergic Neurons by Cytokines
Ling, Z. D., Potter, E. D., Lipton, J. W., & Carvey, P. M. (1998) · Experimental Neurology · doi:10.1006/exnr.1998.6715 · Cited by 292
Neogenesis of cerebellar Purkinje neurons from gene-marked bone marrow cells in vivo
Priller, J., Persons, D. A., Fernández‐Klett, F., Kempermann, G., Kreutzberg, G. W., & Dirnagl, U. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200105103 · Cited by 266
Cellular mechanisms of CNS pericytes
Rucker, H. K., Wynder, H. J., & Thomas, W. E. (2000) · Brain Research Bulletin · doi:10.1016/s0361-9230(99)00260-9 · Cited by 220
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
Schiltz, J. C., & Sawchenko, P. E. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-13-05606.2002 · Cited by 197
Self-citationPolfliet, M. M. J., Zwijnenburg, P. J. G., van Furth, A. M., van der Poll, T., Döpp, E. A., de Lavalette, C. R., van Kesteren-Hendrikx, E. M. L., van Rooijen, N., Dijkstra, C. D., & van den Berg, T. K. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.8.4644 · Cited by 180
The Unexpected G0/G1 Cell Cycle Status of Mobilized Hematopoietic Stem Cells From Peripheral Blood
Uchida, N., He, D., Friera, A. M., Reitsma, M. J., Sasaki, D. T., Chen, B., & Tsukamoto, A. S. (1997) · Blood · doi:10.1182/blood.v89.2.465 · Cited by 177
Kanazawa, H., Ohsawa, K., Sasaki, Y., Kohsaka, S., & Imai, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109218200 · Cited by 174
Endothelial Progenitor Cells for Vascular Regeneration
Asahara, T., & Isner, J. M. (2002) · Stem Cells and Development · doi:10.1089/152581602753658385 · Cited by 139
DIFFERENTIATION OF TRANSPLANTED BONE MARROW CELLS IN THE ADULT MOUSE BRAIN1
Nakano, K., Migita, M., Mochizuki, H., & Shimada, T. (2001) · Transplantation · doi:10.1097/00007890-200106270-00006 · Cited by 125
Adult Bone Marrow Transplantation after Stroke in Adult Rats
Li, Y., Chen, J., & Chopp, M. (2001) · Cell Transplantation · doi:10.3727/000000001783986972 · Cited by 123
The role of perivascular and meningeal macrophages in experimental allergic encephalomyelitis
Polfliet, M. M. J., van de Veerdonk, F. L., Döpp, E. A., van Kesteren-Hendrikx, E. M. L., van Rooijen, N., Dijkstra, C. D., & van den Berg, T. K. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00445-3 · Cited by 112
Shahrara, S., Volin, M. V., Connors, M. A., Haines, G. K., & Koch, A. E. (2002) · Arthritis Research & Therapy · doi:10.1186/ar407 · Cited by 108
Muscle Differentiation: How Two Cells Become One
Taylor, M. V. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00757-1 · Cited by 98
Corti, S. P., Locatelli, F., Strazzer, S., Salani, S., Bo, R. D., Soligo, D. A., Bossolasco, P., Bresolin, N., Scarlato, G., & Comi, G. P. (2002) · Experimental Neurology · doi:10.1006/exnr.2002.8004 · Cited by 82
Bonilla, S., Alarcón, P., Villaverde, R., Aparício, P., Silva, A., & Martı́nez, S. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.01895.x · Cited by 73
Characterization and Expression of a Novel Alternatively Spliced Human Angiopoietin-2
Kim, I., Kim, J.-H., Ryu, Y. S., Jung, S. H., Nah, J. J., & Koh, G. Y. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m910084199 · Cited by 66
Is transdifferentiation in trouble?
Wells, W. A. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200203037 · Cited by 60
Uchida, T., Nakashima, M., Hirota, Y., Miyazaki, Y., Tsukazaki, T., & Shindo, H. (2000) · Annals of the Rheumatic Diseases · doi:10.1136/ard.59.8.607 · Cited by 60
Hahn, C. N., del Pilar Martin, M., Zhou, X.-Y., Mann, L. W., & d’Azzo, A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14880 · Cited by 56
Papadimitriou, J. M., Walters, M. N., & Dean, J. H. (1979) · Critical Reviews in Toxicology · doi:10.3109/10408447909037484 · Cited by 27
Björklund, A., & Svendsen, C. N. (2001) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(01)01980-3 · Cited by 16
Mok, S. S., Clippingdale, A. B., Beyreuther, K. T., Masters, C. L., Barrow, C. J., & Small, D. H. (2000) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20000815)61:4 · Cited by 10
内田, 雄. (2001) · Medical Entomology and Zoology · Cited by 1
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“Similarly, Vallieres reported that many of these cells were in fact perivascular macrophages and that newly-formed parenchymal microglia were found in significant numbers only in the cerebellum and at injury sites (Vallieres and Sawchenko, 2003).”
Background
Metadata
- Authors
- Vallières, L., & Sawchenko, P. E.
- Affiliations
- Salk Institute for Biological Studies (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-06-15
- Volume
- 23
- Issue
- 12
- Pages
- 5197-5207
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6741180
- OpenAlex
- W1894599871
- Cited by
- 245
- References
- 63
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 6 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 11 · 2016: 7 · 2015: 8 · 2014: 17 · 2013: 18 · 2012: 15
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondation pour la Recherche Médicale
- National Institutes of Health (NS21182)
- Canadian Institutes of Health Research
- National Institute of Neurological Disorders and Stroke (NS21182, R37NS021182, R01NS021182)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- bone marrow-derived cells, transdifferentiation, adult neurogenesis, perivascular macrophages, microglia, blood-brain barrier, mesenchymal precursors, brain injury, gene therapy delivery, green fluorescent protein tagging, irradiated mice
- MeSH terms
- Animals, Blood-Brain Barrier, Bone Marrow Cells, Brain, Brain Injuries, Cell Count, Cell Differentiation, Cell Division, Cerebral Decortication, Hematopoietic System, Luminescent Proteins, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Time, Bone Marrow Transplantation, Microglia, Genes, Reporter, Cell Lineage, Green Fluorescent Proteins, Mice
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