Myelin repair and functional recovery mediated by neural cell transplantation in a mouse model of multiple sclerosis
Open accessAbstract
Cellular therapies are becoming a major focus for the treatment of demyelinating diseases such as multiple sclerosis (MS), therefore it is important to identify the most effective cell types that promote myelin repair. Several components contribute to the relative benefits of specific cell types including the overall efficacy of the cell therapy, the reproducibility of treatment, the mechanisms of action of distinct cell types and the ease of isolation and generation of therapeutic populations. A range of distinct cell populations promote functional recovery in animal models of MS including neural stem cells and mesenchymal stem cells derived from different tissues. Each of these cell populations has advantages and disadvantages and likely works through distinct mechanisms. The relevance of such mechanisms to myelin repair in the adult central nervous system is unclear since the therapeutic cells are generally derived from developing animals. Here we describe the isolation and characterization of a population of neural cells from the adult spinal cord that are characterized by the expression of the cell surface glycoprotein NG2. In functional studies, injection of adult NG2(+) cells into mice with ongoing MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) enhanced remyelination in the CNS while the number of CD3(+) T cells in areas of spinal cord demyelination was reduced approximately three-fold. In vivo studies indicated that in EAE, NG2(+) cells stimulated endogenous repair while in vitro they responded to signals in areas of induced inflammation by differentiating into oligodendrocytes. These results suggested that adult NG2(+) cells represent a useful cell population for promoting neural repair in a variety of different conditions including demyelinating diseases such as MS.
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NG2+ MSC-like cells sourced from other biological systems such as liver and central nervous system can generate functional cells for tissue repair.
“These NG2+ MSC-like cells sourced from other biological systems, such as liver and central nervous system (CNS) are found being able to generate functional cells for tissue repair [20, 21].”
From New advances of NG2-expressing cell subset in marrow mesenchymal stem cells as novel therapeutic tools for liver fibrosis/cirrhosis (2024) · cites this paper as [21]
The Introduction and Results (pages unavailable) describe NG2+ cells isolated from adult mouse spinal cord that can generate oligodendrocytes and promote functional recovery and myelin repair in an MS mouse model. The paper does not establish the claim for liver-derived NG2+ cells, and its in vivo repair findings do not show that the transplanted cells themselves generated the repairing cells. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPPWP has been stably used for the isolation of NG2+ cells from multiple adult tissues.
“which has been stably used for the isolation of NG2+ cells from multiple adult tissues [21, 23]”
From New advances of NG2-expressing cell subset in marrow mesenchymal stem cells as novel therapeutic tools for liver fibrosis/cirrhosis (2024) · cites this paper as [21]
The Methods section, “Purification of Mouse Adult Spinal Cord NG2+ Cells Using Percoll Gradient” (page unavailable), describes isolating cells from adult mouse spinal cords. The Results section, “Purification and characterization of Adult Mouse spinal cord-Derived NG2+ cells” (page unavailable), reports that more than 98% of cells were NG2+ by the second passage. Our copy does not identify the procedure as PPWP or establish its stable use across multiple adult tissues. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMost passaged m-NG2/BMMSCs exhibited a diamond-shaped flaky morphology similar to cells isolated from multiple other organs but clearly different from spindle-shaped m-BMMSCs.
“most passaged (P) cells exhibited a diamond-shaped flaky morphology (Fig. 1Aa; Suppl. Fig. S1Bd, pink cartoon marks assumed NG2+ cells), similar to the cells isolated from multiple other organs [21, 23], but those morphologies were clearly different from those of spindle-shaped m-BMMSCs”
From New advances of NG2-expressing cell subset in marrow mesenchymal stem cells as novel therapeutic tools for liver fibrosis/cirrhosis (2024) · cites this paper as [21]
The Results section (page unavailable) says most passaged adult mouse spinal-cord NG2+ cells assumed a rhomboid morphology, consistent with the described diamond shape. The cited paper does not establish that this morphology resembles cells isolated from multiple other organs, nor does it compare these cells with spindle-shaped mouse bone-marrow MSCs. (LLM, conf=0.79)
Experimental — accuracy not yet measuredNG2+ cells promote functional recovery in disease models.
“and promote functional recovery in disease models [21]”
From New advances of NG2-expressing cell subset in marrow mesenchymal stem cells as novel therapeutic tools for liver fibrosis/cirrhosis (2024) · cites this paper as [21]
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Fouraschen, S. M. G., Pan, Q., de Ruiter, P. E., Farid, W. R. R., Kazemier, G., Kwekkeboom, J., Ijzermans, J. N. M., Metselaar, H. J., Tilanus, H. W., de Jonge, J., et al. (2012) · Stem Cells and Development · doi:10.1089/scd.2011.0560 · Cited by 102 · see citing works
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Research works printed but not linked: 59
- [1]Miller RH The promise of stem cells for neural repair Brain Res 2006 1091 258 264 16563359
- [2]Miller RH Bai L Lennon DP Caplan AI The potential of mesenchymal stem cells for neural repair Discov Med 2010 9 236 242 20350491
- [3]Bai L Lennon DP Eaton V Maier K Caplan AI Miller SD Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis Glia 2009 57 1192 1203 19191336 PMC2706928
- [4]Sharp J Keirstead HS Stem cell-based cell replacement strategies for the central nervous system Neurosci Lett 2009 456 107 111 19429144
- [5]Auletta JJ Bartholomew AM Maziarz RT Deans RJ Miller RH Lazarus HM The potential of mesenchymal stromal cells as a novel cellular therapy for multiple sclerosis Immunotherapy 2012 4 529 547 22642335 PMC3381871
- [6]Bai L Lennon DP Caplan AI DeChant A Hecker J Kranso J Hepatocyte growth factor mediates mesenchymal stem cell-induced recovery in multiple sclerosis models Nat Neurosci 2012 15 862 870 22610068 PMC3427471
- [7]Ben-Hur T Cell therapy for multiple sclerosis Neurotherapeutics 2011 8 625 642 21904787 PMC3250283
- [8]Pluchino S Quattrini A Brambilla E Gritti A Salani G Dina G Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis Nature 2003 422 688 694 12700753
- [9]Bassi G Pacelli L Carusone R Zanoncello J Krampera M Adipose-derived stromal cells (ASCs) Transfus Apher Sci 2012 47 193 198 22818214
- [11]Hoffman AM Paxson JA Mazan MR Davis AM Tyagi S Murthy S Lung-derived mesenchymal stromal cell post-transplantation survival, persistence, paracrine expression, and repair of elastase-injured lung Stem Cells Dev 2011 20 1779 1792 21585237 PMC3182034
- [12]Huang Y Chen P Zhang CB Ko GJ Ruiz M Fiorina P Kidney-derived mesenchymal stromal cells modulate dendritic cell function to suppress alloimmune responses and delay allograft rejection Transplantation 2010 90 1307 1311 21048532
- [13]Caplan AI All MSCs are pericytes? Cell Stem Cell 2008 3 229 230 18786406
- [14]Vaculik C Schuster C Bauer W Iram N Pfisterer K Kramer G Human dermis harbors distinct mesenchymal stromal cell subsets J Invest Dermatol 2012 132 563 574 22048731 PMC3278768
- [15]Caplan AI New era of cell-based orthopedic therapies Tissue Eng Part B Rev 2009 15 195 200 19228082 PMC2817662
- [16]Caplan AI Correa D PDGF in bone formation and regeneration: new insights into a novel mechanism involving MSCs J Orthop Res 2011 29 1795 1803 21618276
- [17]Dore-Duffy P Mehedi A Wang X Bradley M Trotter R Gow A Immortalized CNS pericytes are quiescent smooth muscle actin-negative and pluripotent Microvasc Res 2011 82 18 27 21515289 PMC3250068
- [18]Canfield AE Sutton AB Hoyland JA Schor AM Association of thrombospondin-1 with osteogenic differentiation of retinal pericytes in vitro J Cell Sci 1996 109 Pt 2 343 353 8838658
- [19]Doherty MJ Ashton BA Walsh S Beresford JN Grant ME Canfield AE Vascular pericytes express osteogenic potential in vitro and in vivo J Bone Miner Res 1998 13 828 838 9610747
- [20]Dore-Duffy P Pericytes: pluripotent cells of the blood brain barrier Curr Pharm Des 2008 14 1581 1593 18673199
- [21]Hirschi KK D'Amore PA Pericytes in the microvasculature Cardiovasc Res 1996 32 687 698 8915187
- [22]Lundberg C Martinez-Serrano A Cattaneo E McKay RD Bjorklund A Survival, integration, and differentiation of neural stem cell lines after transplantation to the adult rat striatum Exp Neurol 1997 145 342 360 9217071
- [23]Ozerdem U Stallcup WB Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan Angiogenesis 2004 7 269 276 15609081 PMC1350818
- [24]Stallcup WB The NG2 proteoglycan: past insights and future prospects J Neurocytol 2002 31 423 435 14501214
- [25]Nishiyama A Polydendrocytes: NG2 cells with many roles in development and repair of the CNS Neuroscientist 2007 13 62 76 17229976
- [26]Stallcup WB The NG2 antigen, a putative lineage marker: immunofluorescent localization in primary cultures of rat brain Dev Biol 1981 83 154 165 7016634
- [27]Zhu X Hill RA Nishiyama A NG2 cells generate oligodendrocytes and gray matter astrocytes in the spinal cord Neuron Glia Biol 2008 4 19 26 19006598
- [28]Nishiyama A Komitova M Suzuki R Zhu X Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity Nat Rev Neurosci 2009 10 9 22 19096367
- [29]Karadottir R Hamilton NB Bakiri Y Attwell D Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter Nat Neurosci 2008 11 450 456 18311136 PMC2615224
- [30]MacFadyen J Savage K Wienke D Isacke CM Endosialin is expressed on stromal fibroblasts and CNS pericytes in mouse embryos and is downregulated during development Gene Expr Patterns 2007 7 363 369 16965941
- [31]Shepro D Morel NM Pericyte physiology FASEB J 1993 7 1031 1038 8370472
- [32]Edelman DA Jiang Y Tyburski J Wilson RF Steffes C Pericytes and their role in microvasculature homeostasis J Surg Res 2006 135 305 311 16930620
- [33]von Tell D Armulik A Betsholtz C Pericytes and vascular stability Exp Cell Res 2006 312 623 629 16303125
- [34]Balabanov R Dore-Duffy P Role of the CNS microvascular pericyte in the blood-brain barrier J Neurosci Res 1998 53 637 644 9753191
- [35]Ballabh P Braun A Nedergaard M The blood-brain barrier: an overview: structure, regulation, and clinical implications Neurobiol Dis 2004 16 1 13 15207256
- [36]Dore-Duffy P Katychev A Wang X Van Buren E CNS micro-vascular pericytes exhibit multipotential stem cell activity J Cereb Blood Flow Metab 2006 26 613 624 16421511
- [37]Wight PA Duchala CS Shick HE Gudz TI Macklin WB Expression of a myelin proteolipid protein (Plp)-lacZ transgene is reduced in both the CNS and PNS of Plp(jp) mice Neurochem Res 2007 32 343 351 17191136 PMC1976413
- [38]Garbelli R Zucca I Milesi G Mastropietro A D'Incerti L Tassi L Combined 7-T MRI and histopathologic study of normal and dysplastic samples from patients with TLE Neurology 2011 76 1177 1185 21444904
- [39]Sun HS French RJ Feng ZP A method for identifying viable and damaged neurons in adult mouse brain slices Acta Histochem 2009 111 531 537 19203782
- [40]Jariyapongskul A Nakano A Yamaguchi S Nageswari K Niimi H Maturity of pericytes in cerebral neocapillaries induced by growth factors: fluorescence immuno-histochemical analysis using confocal laser microscopy Clin Hemorheol Microcirc 2003 29 417 421 14724369
- [41]Sims DE The pericyte--a review Tissue Cell 1986 18 153 174 3085281
- [42]Orlidge A D'Amore PA Cell specific effects of glycosaminoglycans on the attachment and proliferation of vascular wall components Microvasc Res 1986 31 41 53 3959914
- [43]Yang Z Watanabe M Nishiyama A Optimization of oligodendrocyte progenitor cell culture method for enhanced survival J Neurosci Methods 2005 149 50 56 15975663
- [44]Kucharova K Chang Y Boor A Yong VW Stallcup WB Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord J Neuroinflammation 2011 8 158 22078261 PMC3229456
- [45]Tripathi RB Rivers LE Young KM Jamen F Richardson WD NG2 glia generate new oligodendrocytes but few astrocytes in a murine experimental autoimmune encephalomyelitis model of demyelinating disease J Neurosci 2010 30 16383 16390 21123584 PMC3063541
- [46]Pringle N Collarini EJ Mosley MJ Heldin CH Westermark B Richardson WD PDGF A chain homodimers drive proliferation of bipotential (O-2A) glial progenitor cells in the developing rat optic nerve EMBO J 1989 8 1049 1056 2545439 PMC400913
- [47]Tsai HH Macklin WB Miller RH Distinct modes of migration position oligodendrocyte precursors for localized cell division in the developing spinal cord J Neurosci Res 2009 87 3320 3330 19301427 PMC2861839
- [48]Kaplan JM Youd ME Lodie TA Immunomodulatory activity of mesenchymal stem cells Curr Stem Cell Res Ther 2011 6 297 316 21190531
- [49]Payne NL Sun G Herszfeld D Tat-Goh PA Verma PJ Parkington HC Comparative study on the therapeutic potential of neurally differentiated stem cells in a mouse model of multiple sclerosis PLoS One 2012 7 e35093 22514711 PMC3325988
- [50]Miller RH Bai L Translating stem cell therapies to the clinic Neurosci Lett 2012 519 87 92 22306614
- [51]Busch SA Horn KP Cuascut FX Hawthorne AL Bai L Miller RH Adult NG2+ cells are permissive to neurite outgrowth and stabilize sensory axons during macrophage-induced axonal dieback after spinal cord injury J Neurosci 2010 30 255 265 20053907 PMC2823089
- [52]Whitman LM Blanc CA Schaumburg CS Rowitch DH Lane TE Olig1 function is required for remyelination potential of transplanted neural progenitor cells in a model of viral-induced demyelination Exp Neurol 2012 235 380 387 22449475 PMC3350784
- [53]Kondo T Raff M Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells Science 2000 289 1754 1757 10976069
- [54]Nishiyama A Yang Z Butt A Astrocytes and NG2-glia: what's in a name? J Anat 2005 207 687 693 16367796 PMC1571571
- [55]Dincman TA Beare JE Ohri SS Whittemore SR Isolation of cortical mouse oligodendrocyte precursor cells J Neurosci Methods 2012 209 219 226 22743801 PMC3407963
- [56]Staugaitis SM Trapp BD NG2-positive glia in the human central nervous system Neuron Glia Biol 2009 5 35 44 19785924
- [57]Carlesi C Pasquali L Piazza S Lo Gerfo A Caldarazzo Ienco E Alessi R Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis Arch Ital Biol 2011 149 151 167 21412722
- [58]Naganska E Matyja E Amyotrophic lateral sclerosis - looking for pathogenesis and effective therapy Folia Neuropathol 2011 49 1 13 21455838
- [59]Lepore AC Dejea C Carmen J Rauck B Kerr DA Sofroniew MV Selective ablation of proliferating astrocytes does not affect disease outcome in either acute or chronic models of motor neuron degeneration Exp Neurol 2008 211 423 432 18410928 PMC9152669
- [60]Kang SH Fukaya M Yang JK Rothstein JD Bergles DE NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurode-generation Neuron 2010 68 668 681 21092857 PMC2989827
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Sorted by citations
Fouraschen, S. M. G., Pan, Q., de Ruiter, P. E., Farid, W. R. R., Kazemier, G., Kwekkeboom, J., Ijzermans, J. N. M., Metselaar, H. J., Tilanus, H. W., de Jonge, J., et al. (2012) · Stem Cells and Development · doi:10.1089/scd.2011.0560 · Cited by 102 · see citing works
Zhang, H., Siegel, C. T., Shuai, L., Lai, J., Zeng, L., Zhang, Y., Lai, X., Bie, P., & Bai, L. (2016) · Scientific Reports · doi:10.1038/srep21783 · Cited by 30 · see citing works
Self-citationHu, D., Lai, J., Chen, Q., & Bai, L. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03817-x · Cited by 6 · see citing works
“These NG2 + MSC-like cells sourced from other biological systems, such as liver and central nervous system (CNS) are found being able to generate functional cells for tissue repair [20, 21].”
BackgroundMethodResultInfluentialSelf-citation
- Authors
- Bai, L., Hecker, J., Kerstetter, A., & Miller, R. H.
- Affiliations
- Case Western Reserve University (US)
- Corresponding author
- Bai, Lianhua
- Miller, Robert H.
- Venue
- Neuroscience Bulletin
- Published
- 2013-03-08
- Volume
- 29
- Issue
- 2
- Pages
- 239-250
- ISSN
- 1995-8218 (ISSN-L)
- 1673-7067
- PMC
- PMC4117317
- OpenAlex
- W2071145324
- Cited by
- 30
- References
- 1
- Citations by year
- 2024: 5 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 6 · 2013: 2 · 2012: 1
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuroscience Bulletin (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS 030800, R01NS030800, NS077942, R01NS077942)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- multiple sclerosis, remyelination, neural transplantation, oligodendrocyte precursor cells, adult spinal cord, experimental autoimmune encephalomyelitis, MOG35-55, oligodendrocyte differentiation, demyelination, T cell depletion, cell therapy, demyelinating disease
- MeSH terms
- Chondroitin Sulfate Proteoglycan 4, Animals, Animals, Newborn, Antigens, Bromodeoxyuridine, Cells, Cultured, Disease Models, Animal, Female, Glial Fibrillary Acidic Protein, Male, Mice, Inbred C57BL, Mice, Transgenic, Multiple Sclerosis, Neurons, Oligodendroglia, Organ Culture Techniques, Peptide Fragments, Proteoglycans, Spinal Cord, Time Factors, Culture Media, Conditioned, CD3 Complex, Cell Transplantation, Myelin Proteolipid Protein, Recovery of Function, Proto-Oncogene Proteins c-sis, Green Fluorescent Proteins, Mice, Myelin-Oligodendrocyte Glycoprotein
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