Advertisement

Stem Cell Reviews and Reports

, Volume 11, Issue 4, pp 621–634 | Cite as

Controversial Role of Toll-like Receptor 4 in Adult Stem Cells

  • Marie Zeuner
  • Karen Bieback
  • Darius Widera
Article

Abstract

Adult or somatic stem cells are tissue-resident cells with the ability to proliferate, exhibit self-maintenance as well as to generate new cells with the principal phenotypes of the tissue in response to injury or disease. Due to their easy accessibility and their potential use in regenerative medicine, adult stem cells raise the hope for future personalisable therapies. After infection or during injury, they are exposed to broad range of pathogen or damage-associated molecules leading to changes in their proliferation, migration and differentiation. The sensing of such damage and infection signals is mostly achieved by Toll-Like Receptors (TLRs) with Toll-like receptor 4 being responsible for recognition of bacterial lipopolysaccharides (LPS) and endogenous danger-associated molecular patterns (DAMPs). In this review, we examine the current state of knowledge on the TLR4-mediated signalling in different adult stem cell populations. Specifically, we elaborate on the role of TLR4 and its ligands on proliferation, differentiation and migration of mesenchymal stem cells, hematopoietic stem cells as well as neural stem cells. Finally, we discuss conceptual and technical pitfalls in investigation of TLR4 signalling in stem cells.

Keywords

TLR4 LPS Adult Stem Cells Mesenchymal Stem Cells Hematopoietic Stem Cells Neural Stem Cells NF-kappaB IRF3 DAMPs PAMPs 

Notes

Acknowledgment

MZ and DW are supported by the DFG (Grant WI4318/2-1).

Conflict of Interests

The authors declare no conflict of interests

References

  1. 1.
    Anderson, K. V., Jürgens, G., & Nüsslein-Volhard, C. (1985). Establishment of dorsal-ventral polarity in the Drosophila embryo: Genetic studies on the role of the Toll gene product. Cell, 42, 779–789.PubMedGoogle Scholar
  2. 2.
    Morisato, D., & Anderson, K. V. (1994). The spatzle gene encodes a component of the extracellular signaling pathway establishing the dorsal-ventral pattern of the Drosophila embryo. Cell, 76, 677–688.PubMedGoogle Scholar
  3. 3.
    Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J. M., & Hoffmann, J. A. (1996). The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell, 86, 973–983.PubMedGoogle Scholar
  4. 4.
    Ozinsky, A., Underhill, D. M., Fontenot, J. D., et al. (2000). The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors. Proceedings of the National Academy of Sciences of the United States of America, 97, 13766–13771.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Miyake, K. (2007). Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Seminars in Immunology, 19, 3–10.PubMedGoogle Scholar
  6. 6.
    Botos, I., Segal David, M., & Davies David, R. (2011). The structural biology of Toll-like receptors. Structure, 19, 447–459.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J., & Gusovsky, F. (1999). Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. Journal of Biological Chemistry, 274, 10689–10692.PubMedGoogle Scholar
  8. 8.
    Abreu, M. T., Vora, P., Faure, E., Thomas, L. S., Arnold, E. T., & Arditi, M. (2001). Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. Journal of Immunology, 167, 1609–1616.Google Scholar
  9. 9.
    Frantz, S., Kobzik, L., Kim, Y. D., et al. (1999). Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. Journal of Clinical Investigation, 104, 271–280.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Lehnardt, S., Lachance, C., Patrizi, S., et al. (2002). The Toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. Journal of Neuroscience, 22, 2478–2486.PubMedGoogle Scholar
  11. 11.
    Olson, J. K., & Miller, S. D. (2004). Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. Journal of Immunology, 173, 3916–3924.Google Scholar
  12. 12.
    Bowman, C. C., Rasley, A., Tranguch, S. L., & Marriott, I. (2003). Cultured astrocytes express Toll-like receptors for bacterial products. Glia, 43, 281–291.PubMedGoogle Scholar
  13. 13.
    Tang, S. C., Arumugam, T. V., Xu, X., et al. (2007). Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proceedings of the National Academy of Sciences of the United States of America, 104, 13798–13803.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Tang, S. C., Lathia, J. D., Selvaraj, P. K., et al. (2008). Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal. Experimental Neurology, 213, 114–121.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Esplin, B. L., Shimazu, T., Welner, R. S., et al. (2011). Chronic exposure to a TLR ligand injures hematopoietic stem cells. Journal of Immunology, 186, 5367–5375.Google Scholar
  16. 16.
    He, J., Xiao, Z., Chen, X., et al. (2010). The expression of functional Toll-like receptor 4 is associated with proliferation and maintenance of stem cell phenotype in endothelial progenitor cells (EPCs). Journal of Cellular Biochemistry, 111, 179–186.PubMedGoogle Scholar
  17. 17.
    Li, C., Li, B., Dong, Z., et al. (2014). Lipopolysaccharide differentially affects the osteogenic differentiation of periodontal ligament stem cells and bone marrow mesenchymal stem cells through Toll-like receptor 4 mediated nuclear factor kappaB pathway. Stem Cell Research & Therapy, 5, 67.Google Scholar
  18. 18.
    Hwang, S. H., Cho, H. K., Park, S. H., et al. (2014). Toll like receptor 3 & 4 responses of human turbinate derived mesenchymal stem cells: stimulation by double stranded RNA and lipopolysaccharide. PloS One, 9, e101558.PubMedCentralPubMedGoogle Scholar
  19. 19.
    Raicevic, G., Rouas, R., Najar, M., et al. (2010). Inflammation modifies the pattern and the function of Toll-like receptors expressed by human mesenchymal stromal cells. Human Immunology, 71, 235–244.PubMedGoogle Scholar
  20. 20.
    He, W., Wang, Z., Luo, Z., et al. (2015). LPS promote the odontoblastic differentiation of human dental pulp stem cells via MAPK signaling pathway. Journal of Cellular Physiology, 230, 554–561.PubMedGoogle Scholar
  21. 21.
    Shechter, R., Ronen, A., Rolls, A., et al. (2008). Toll-like receptor 4 restricts retinal progenitor cell proliferation. Journal of Cell Biology, 183, 393–400.PubMedCentralPubMedGoogle Scholar
  22. 22.
    Rolls, A., Shechter, R., London, A., et al. (2007). Toll-like receptors modulate adult hippocampal neurogenesis. Nature Cell Biology, 9, 1081–1088.PubMedGoogle Scholar
  23. 23.
    Okun, E., Barak, B., Saada-Madar, R., et al. (2012). Evidence for a developmental role for TLR4 in learning and memory. PloS One, 7, e47522.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Pradillo, J. M., Fernandez-Lopez, D., Garcia-Yebenes, I., et al. (2009). Toll-like receptor 4 is involved in neuroprotection afforded by ischemic preconditioning. Journal of Neurochemistry, 109, 287–294.PubMedGoogle Scholar
  25. 25.
    Okun, E., Griffioen, K. J., & Mattson, M. P. (2011). Toll-like receptor signaling in neural plasticity and disease. Trends in Neurosciences, 34, 269–281.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Mai, C. W., Kang, Y. B., & Pichika, M. R. (2013). Should a Toll-like receptor 4 (TLR-4) agonist or antagonist be designed to treat cancer? TLR-4: its expression and effects in the ten most common cancers. Onco Targets and therapy, 6, 1573–1587.Google Scholar
  27. 27.
    Watanabe, S., Kumazawa, Y., & Inoue, J. (2013). Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. PloS One, 8, e60078.PubMedCentralPubMedGoogle Scholar
  28. 28.
    Marsh, B. J., Williams-Karnesky, R. L., & Stenzel-Poore, M. P. (2009). Toll-like receptor signaling in endogenous neuroprotection and stroke. Neuroscience, 158, 1007–1020.PubMedCentralPubMedGoogle Scholar
  29. 29.
    Raetz, C. R. H., & Whitfield, C. (2002). Lipopolysaccharide endotoxins. Annual Review of Biochemistry, 71, 635–700.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Galanos, C., LÜDeritz, O., Rietschel, E. T., et al. (1985). Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities. European Journal of Biochemistry, 148, 1–5.PubMedGoogle Scholar
  31. 31.
    Si, S. (2004). Akashi S, Yamada T, et al. Lipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll‐like receptor 4 (TLR4)‐MD‐2 and ligand‐induced TLR4 oligomerization. International Immunology, 16, 961–969.Google Scholar
  32. 32.
    Rietschel, E., Wollenweber, H.-W., Zähringer, U., & Lüderitz, O. (1982). Lipid A, the lipid component of bacterial lipopolysaccharides: Relation of chemical structure to biological activity. Klinische Wochenschrift, 60, 705–709.PubMedGoogle Scholar
  33. 33.
    Gutschow, M. V., Hughey, J. J., Ruggero, N. A., Bajar, B. T., Valle, S. D., & Covert, M. W. (2013). Single-cell and population NF-kappaB dynamic responses depend on lipopolysaccharide preparation. PloS One, 8, e53222.PubMedCentralPubMedGoogle Scholar
  34. 34.
    Miller, S. I., Ernst, R. K., & Bader, M. W. (2005). LPS, TLR4 and infectious disease diversity. Nature Reviews Microbiology, 3, 36–46.PubMedGoogle Scholar
  35. 35.
    Sloane, J. A., Blitz, D., Margolin, Z., & Vartanian, T. (2010). A clear and present danger: endogenous ligands of Toll-like receptors. Neuromolecular Medicine, 12, 149–163.PubMedCentralPubMedGoogle Scholar
  36. 36.
    Erridge, C. (2010). Endogenous ligands of TLR2 and TLR4: agonists or assistants? Journal of Leukocyte Biology, 87, 989–999.PubMedGoogle Scholar
  37. 37.
    Mendelson, A., & Frenette, P. S. (2014). Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nature Medicine, 20, 833–846.PubMedCentralPubMedGoogle Scholar
  38. 38.
    Boiko, J. R., & Borghesi, L. (2012). Hematopoiesis sculpted by pathogens: Toll-like receptors and inflammatory mediators directly activate stem cells. Cytokine, 57, 1–8.PubMedCentralPubMedGoogle Scholar
  39. 39.
    Nagai, Y., Garrett, K. P., Ohta, S., et al. (2006). Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity, 24, 801–812.PubMedCentralPubMedGoogle Scholar
  40. 40.
    Ichii, M., Shimazu, T., Welner, R. S., et al. (2010). Functional diversity of stem and progenitor cells with B-lymphopoietic potential. Immunology Reviews, 237, 10–21.Google Scholar
  41. 41.
    Burberry, A., Zeng, M. Y., Ding, L., et al. (2014). Infection mobilizes hematopoietic stem cells through cooperative NOD-like receptor and Toll-like receptor signaling. Cell Host & Microbe, 15, 779–791.Google Scholar
  42. 42.
    Baldridge, M. T., King, K. Y., & Goodell, M. A. (2011). Inflammatory signals regulate hematopoietic stem cells. Trends in Immunology, 32, 57–65.PubMedCentralPubMedGoogle Scholar
  43. 43.
    Chambers, S. M., Shaw, C. A., Gatza, C., Fisk, C. J., Donehower, L. A., & Goodell, M. A. (2007). Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biology, 5, e201.PubMedCentralPubMedGoogle Scholar
  44. 44.
    Boettcher, S., Ziegler, P., Schmid, M. A., et al. (2012). Cutting edge: LPS-induced emergency myelopoiesis depends on TLR4-expressing nonhematopoietic cells. Journal of Immunology, 188, 5824–5828.Google Scholar
  45. 45.
    Megias, J., Yanez, A., Moriano, S., O'Connor, J. E., Gozalbo, D., & Gil, M. L. (2012). Direct Toll-like receptor-mediated stimulation of hematopoietic stem and progenitor cells occurs in vivo and promotes differentiation toward macrophages. Stem Cells, 30, 1486–1495.PubMedGoogle Scholar
  46. 46.
    Shi, X., Siggins, R. W., Stanford, W. L., Melvan, J. N., Basson, M. D., & Zhang, P. (2013). Toll-like receptor 4/stem cell antigen 1 signaling promotes hematopoietic precursor cell commitment to granulocyte development during the granulopoietic response to Escherichia coli bacteremia. Infection and Immunity, 81, 2197–2205.PubMedCentralPubMedGoogle Scholar
  47. 47.
    Pittenger, M. F., Mackay, A. M., Beck, S. C., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143–147.PubMedGoogle Scholar
  48. 48.
    Zuk, P. A., Zhu, M., Ashjian, P., et al. (2002). Human adipose tissue is a source of multipotent stem cells. Molecular Biology of the Cell, 13, 4279–4295.PubMedCentralPubMedGoogle Scholar
  49. 49.
    Delorme, B., Nivet, E., Gaillard, J., et al. (2010). The human nose harbors a niche of olfactory ectomesenchymal stem cells displaying neurogenic and osteogenic properties. Stem Cells and Development, 19, 853–866.PubMedGoogle Scholar
  50. 50.
    Diaz-Solano, D., Wittig, O., Ayala-Grosso, C., Pieruzzini, R., & Cardier, J. E. (2012). Human olfactory mucosa multipotent mesenchymal stromal cells promote survival, proliferation, and differentiation of human hematopoietic cells. Stem Cells and Development, 21, 3187–3196.PubMedCentralPubMedGoogle Scholar
  51. 51.
    Hwang, S. H., Kim, S. Y., Park, S. H., et al. (2012). Human inferior turbinate: an alternative tissue source of multipotent mesenchymal stromal cells. Otolaryngology and Head and Neck Surgery, 147, 568–574.Google Scholar
  52. 52.
    Crisan, M., Yap, S., Casteilla, L., et al. (2008). A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell, 3, 301–313.PubMedGoogle Scholar
  53. 53.
    Dominici, M., Le Blanc, K., Mueller, I., et al. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315–317.PubMedGoogle Scholar
  54. 54.
    Salem, H. K., & Thiemermann, C. (2010). Mesenchymal stromal cells: current understanding and clinical status. Stem Cells, 28, 585–596.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Lalu, M. M., McIntyre, L., Pugliese, C., et al. (2012). Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PloS One, 7, e47559.PubMedCentralPubMedGoogle Scholar
  56. 56.
    Kinzebach, S., & Bieback, K. (2013). Expansion of Mesenchymal Stem/Stromal cells under xenogenic-free culture conditions. Advances in Biochemical Engineering/Biotechnology, 129, 33–57.PubMedGoogle Scholar
  57. 57.
    Sharma, R. R., Pollock, K., Hubel, A., & McKenna, D. (2014). Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices. Transfusion, 54, 1418–1437.PubMedGoogle Scholar
  58. 58.
    Prockop, D. J. (2007). “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clinical Pharmacology and Therapeutics, 82, 241–243.PubMedGoogle Scholar
  59. 59.
    Bieback, K., Wuchter, P., Besser, D., et al. (2012). Mesenchymal stromal cells (MSCs): science and f(r)iction. Journal of Molecular Medicine (Berl), 90, 773–782.Google Scholar
  60. 60.
    Maumus, M., Jorgensen, C., & Noel, D. (2013). Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: role of secretome and exosomes. Biochimie, 95, 2229–2234.PubMedGoogle Scholar
  61. 61.
    van den Akker, F., de Jager, S. C., & Sluijter, J. P. (2013). Mesenchymal stem cell therapy for cardiac inflammation: immunomodulatory properties and the influence of Toll-like receptors. Mediators of Inflammation, 2013, 181020.PubMedCentralPubMedGoogle Scholar
  62. 62.
    Kyurkchiev, D., Bochev, I., Ivanova-Todorova, E., et al. (2014). Secretion of immunoregulatory cytokines by mesenchymal stem cells. World Journal Stem Cells, 6, 552–570.Google Scholar
  63. 63.
    Liotta, F., Angeli, R., Cosmi, L., et al. (2008). Toll-like receptors 3 and 4 are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing Notch signaling. Stem Cells, 26, 279–289.PubMedGoogle Scholar
  64. 64.
    Shi, L., Wang, J. S., Liu, X. M., Hu, X. Y., & Fang, Q. (2007). Upregulated functional expression of Toll like receptor 4 in mesenchymal stem cells induced by lipopolysaccharide. Chinese Medical Journal, 120, 1685–1688.PubMedGoogle Scholar
  65. 65.
    Pevsner-Fischer, M., Morad, V., Cohen-Sfady, M., et al. (2007). Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood, 109, 1422–1432.PubMedGoogle Scholar
  66. 66.
    Opitz, C. A., Litzenburger, U. M., Lutz, C., et al. (2009). Toll-like receptor engagement enhances the immunosuppressive properties of human bone marrow-derived mesenchymal stem cells by inducing indoleamine-2,3-dioxygenase-1 via interferon-beta and protein kinase R. Stem Cells, 27, 909–919.PubMedGoogle Scholar
  67. 67.
    Yan, H., Wu, M., Yuan, Y., Wang, Z. Z., Jiang, H., & Chen, T. (2014). Priming of Toll-like receptor 4 pathway in mesenchymal stem cells increases expression of B cell activating factor. Biochemical and Biophysical Research Communications, 448, 212–217.PubMedGoogle Scholar
  68. 68.
    Chen, X., Zhang, Z. Y., Zhou, H., & Zhou, G. W. (2014). Characterization of mesenchymal stem cells under the stimulation of Toll-like receptor agonists. Development, Growth & Differentiation, 56, 233–244.Google Scholar
  69. 69.
    Zhang, L., Liu, D., Pu, D., et al. (2015). The role of Toll-like receptor 3 and 4 in regulating the function of mesenchymal stem cells isolated from umbilical cord. International Journal of Molecular Medicine, 35, 1003–1010.PubMedGoogle Scholar
  70. 70.
    DelaRosa, O., & Lombardo, E. (2010). Modulation of adult mesenchymal stem cells activity by Toll-like receptors: implications on therapeutic potential. Mediators of Inflammation, 2010, 865601.PubMedCentralPubMedGoogle Scholar
  71. 71.
    Wang, Z. J., Zhang, F. M., Wang, L. S., Yao, Y. W., Zhao, Q., & Gao, X. (2009). Lipopolysaccharides can protect mesenchymal stem cells (MSCs) from oxidative stress-induced apoptosis and enhance proliferation of MSCs via Toll-like receptor(TLR)-4 and PI3K/Akt. Cell Biology International, 33, 665–674.PubMedGoogle Scholar
  72. 72.
    Giuliani, M., Bennaceur-Griscelli, A., Nanbakhsh, A., et al. (2014). TLR ligands stimulation protects MSC from NK killing. Stem Cells, 32, 290–300.PubMedGoogle Scholar
  73. 73.
    Mei, Y. B., Zhou, W. Q., Zhang, X. Y., Wei, X. J., & Feng, Z. C. (2013). Lipopolysaccharides shapes the human Wharton”s jelly-derived mesenchymal stem cells in vitro. Cellular Physiology and Biochemistry, 32, 390–401.PubMedGoogle Scholar
  74. 74.
    Hwa Cho, H., Bae, Y. C., & Jung, J. S. (2006). Role of Toll-like receptors on human adipose-derived stromal cells. Stem Cells, 24, 2744–2752.PubMedGoogle Scholar
  75. 75.
    Mo, I. F., Yip, K. H., Chan, W. K., Law, H. K., Lau, Y. L., & Chan, G. C. (2008). Prolonged exposure to bacterial toxins downregulated expression of Toll-like receptors in mesenchymal stromal cell-derived osteoprogenitors. BMC Cell Biology, 9, 52.PubMedCentralPubMedGoogle Scholar
  76. 76.
    Wang, Y., Abarbanell, A. M., Herrmann, J. L., et al. (2010). TLR4 inhibits mesenchymal stem cell (MSC) STAT3 activation and thereby exerts deleterious effects on MSC-mediated cardioprotection. PloS One, 5, e14206.PubMedCentralPubMedGoogle Scholar
  77. 77.
    Raicevic, G., Najar, M., Pieters, K., et al. (2012). Inflammation and Toll-like receptor ligation differentially affect the osteogenic potential of human mesenchymal stromal cells depending on their tissue origin. Tissue Engineering Part A, 18, 1410–1418.PubMedGoogle Scholar
  78. 78.
    Lei, J., Wang, Z., Hui, D., et al. (2011). Ligation of TLR2 and TLR4 on murine bone marrow-derived mesenchymal stem cells triggers differential effects on their immunosuppressive activity. Cellular Immunology, 271, 147–156.PubMedGoogle Scholar
  79. 79.
    Tomchuck, S. L., Zwezdaryk, K. J., Coffelt, S. B., Waterman, R. S., Danka, E. S., & Scandurro, A. B. (2008). Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells, 26, 99–107.PubMedCentralPubMedGoogle Scholar
  80. 80.
    Lombardo, E., DelaRosa, O., Mancheno-Corvo, P., Menta, R., Ramirez, C., & Buscher, D. (2009). Toll-like receptor-mediated signaling in human adipose-derived stem cells: implications for immunogenicity and immunosuppressive potential. Tissue Engineering Part A, 15, 1579–1589.PubMedGoogle Scholar
  81. 81.
    Tomic, S., Djokic, J., Vasilijic, S., et al. (2011). Immunomodulatory properties of mesenchymal stem cells derived from dental pulp and dental follicle are susceptible to activation by Toll-like receptor agonists. Stem Cells and Development, 20, 695–708.PubMedGoogle Scholar
  82. 82.
    Covacu, R., Arvidsson, L., Andersson, Å., et al. (2009). TLR Activation Induces TNF-α Production from Adult Neural Stem/Progenitor Cells. The Journal of Immunology, 182, 6889–6895.PubMedGoogle Scholar
  83. 83.
    Schuster, A., Klotz, M., Schwab, T., et al. (2014). Maintenance of the enteric stem cell niche by bacterial lipopolysaccharides? Evidence and perspectives. Journal of Cellular and Molecular Medicine, 18, 1429–1443.PubMedCentralPubMedGoogle Scholar
  84. 84.
    Su, Y., Zhang, Z., Trautmann, K., Xu, S., & Schluesener, H. J. (2005). TLR and NOD2 ligands induce cell proliferation in the rat intact spinal cord. Journal of Neuropathology and Experimental Neurology, 64, 991–997.PubMedGoogle Scholar
  85. 85.
    Wu, J. P., Kuo, J. S., Liu, Y. L., & Tzeng, S. F. (2000). Tumor necrosis factor-alpha modulates the proliferation of neural progenitors in the subventricular/ventricular zone of adult rat brain. Neuroscience Letters, 292, 203–206.PubMedGoogle Scholar
  86. 86.
    Wong, G., Goldshmit, Y., & Turnley, A. M. (2004). Interferon-gamma but not TNF alpha promotes neuronal differentiation and neurite outgrowth of murine adult neural stem cells. Experimental Neurology, 187, 171–177.PubMedGoogle Scholar
  87. 87.
    Widera, D., Mikenberg, I., Elvers, M., Kaltschmidt, C., & Kaltschmidt, B. (2006). Tumor necrosis factor alpha triggers proliferation of adult neural stem cells via IKK/NF-kappaB signaling. BMC Neuroscience, 7, 64.PubMedCentralPubMedGoogle Scholar
  88. 88.
    Rubio-Araiz, A., Arevalo-Martin, A., Gomez-Torres, O., et al. (2008). The endocannabinoid system modulates a transient TNF pathway that induces neural stem cell proliferation. Molecular and Cellular Neuroscience, 38, 374–380.PubMedGoogle Scholar
  89. 89.
    Tarassishin, L., Bauman, A., Suh, H. S., & Lee, S. C. (2013). Anti-viral and anti-inflammatory mechanisms of the innate immune transcription factor interferon regulatory factor 3: relevance to human CNS diseases. Journal of Neuroimmune Pharmacology, 8, 132–144.PubMedGoogle Scholar
  90. 90.
    Lum, M., Croze, E., Wagner, C., McLenachan, S., Mitrovic, B., & Turnley, A. M. (2009). Inhibition of neurosphere proliferation by IFNgamma but not IFNbeta is coupled to neuronal differentiation. Journal of Neuroimmunology, 206, 32–38.PubMedGoogle Scholar
  91. 91.
    Cacci, E., Claasen, J. H., & Kokaia, Z. (2005). Microglia-derived tumor necrosis factor-alpha exaggerates death of newborn hippocampal progenitor cells in vitro. Journal of Neuroscience Research, 80, 789–797.PubMedGoogle Scholar
  92. 92.
    Koo, J. W., Russo, S. J., Ferguson, D., Nestler, E. J., & Duman, R. S. (2010). Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proceedings of the National Academy of Sciences of the United States of America, 107, 2669–2674.PubMedCentralPubMedGoogle Scholar
  93. 93.
    Martino, G., & Pluchino, S. (2007). Neural stem cells: guardians of the brain. Nature Cell Biology, 9, 1031–1034.PubMedGoogle Scholar
  94. 94.
    Wang, P. P., Xie, D. Y., Liang, X. J., et al. (2012). HGF and direct mesenchymal stem cells contact synergize to inhibit hepatic stellate cells activation through TLR4/NF-kB pathway. PloS One, 7, e43408.PubMedCentralPubMedGoogle Scholar
  95. 95.
    Edelman, D. A., Jiang, Y., Tyburski, J. G., Wilson, R. F., & Steffes, C. P. (2007). Cytokine production in lipopolysaccharide-exposed rat lung pericytes. Journal of Trauma, 62, 89–93.PubMedGoogle Scholar
  96. 96.
    Guijarro-Munoz, I., Compte, M., Alvarez-Cienfuegos, A., Alvarez-Vallina, L., & Sanz, L. (2014). Lipopolysaccharide activates Toll-like receptor 4 (TLR4)-mediated NF-kappaB signaling pathway and proinflammatory response in human pericytes. Journal of Biological Chemistry, 289, 2457–2468.PubMedCentralPubMedGoogle Scholar
  97. 97.
    Xiao, Z., Yang, M., Fang, L., et al. (2012). Extracellular nucleotide inhibits cell proliferation and negatively regulates Toll-like receptor 4 signalling in human progenitor endothelial cells. Cell Biology International, 36, 625–633.PubMedGoogle Scholar
  98. 98.
    Yamada, M., Kubo, H., Ishizawa, K., Kobayashi, S., Shinkawa, M., & Sasaki, H. (2005). Increased circulating endothelial progenitor cells in patients with bacterial pneumonia: evidence that bone marrow derived cells contribute to lung repair. Thorax, 60, 410–413.PubMedCentralPubMedGoogle Scholar
  99. 99.
    Mao, S. Z., Ye, X., Liu, G., Song, D., & Liu, S. F. (2014). An obligatory role of NF-kappaB in mediating bone marrow derived endothelial progenitor cell recruitment and proliferation following endotoxemic multiple organ injury in mice. PloS One, 9, e111087.PubMedCentralPubMedGoogle Scholar
  100. 100.
    Neal, M. D., Sodhi, C. P., Jia, H., et al. (2012). Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis. Journal of Biological Chemistry, 287, 37296–37308.PubMedCentralPubMedGoogle Scholar
  101. 101.
    He, W., Qu, T., Yu, Q., et al. (2013). LPS induces IL-8 expression through TLR4, MyD88, NF-kappaB and MAPK pathways in human dental pulp stem cells. International Endodontic Journal, 46, 128–136.PubMedGoogle Scholar
  102. 102.
    He, W., Wang, Z., Zhou, Z., et al. (2014). Lipopolysaccharide enhances Wnt5a expression through Toll-like receptor 4, myeloid differentiating factor 88, phosphatidylinositol 3-OH kinase/AKT and nuclear factor kappa B pathways in human dental pulp stem cells. Journal of Endodontia, 40, 69–75.Google Scholar
  103. 103.
    Li, D., Fu, L., Zhang, Y., et al. (2014). The effects of LPS on adhesion and migration of human dental pulp stem cells in vitro. Journal of Dentistry, 42, 1327–1334.PubMedGoogle Scholar
  104. 104.
    Feng, X., Feng, G., Xing, J., et al. (2014). Repeated lipopolysaccharide stimulation promotes cellular senescence in human dental pulp stem cells (DPSCs). Cell and Tissue Research, 356, 369–380.PubMedGoogle Scholar
  105. 105.
    Kim, J. C., Lee, Y. H., Yu, M. K., et al. (2012). Anti-inflammatory mechanism of PPARgamma on LPS-induced pulp cells: role of the ROS removal activity. Archives of Oral Biology, 57, 392–400.PubMedGoogle Scholar
  106. 106.
    Chatzivasileiou, K., Lux, C. A., Steinhoff, G., & Lang, H. (2013). Dental follicle progenitor cells responses to Porphyromonas gingivalis LPS. Journal of Cellular and Molecular Medicine, 17, 766–773.PubMedCentralPubMedGoogle Scholar
  107. 107.
    Zhang, J., Zhang, Y., Lv, H., et al. (2013). Human stem cells from the apical papilla response to bacterial lipopolysaccharide exposure and anti-inflammatory effects of nuclear factor I C. Journal of Endodontia, 39, 1416–1422.Google Scholar
  108. 108.
    Chamila Prageeth Pandula, P. K., Samaranayake, L. P., Jin, L. J., & Zhang, C. (2014). Periodontal ligament stem cells: an update and perspectives. Journal of Investigative and Clinical Dentistry, 5, 81–90.PubMedGoogle Scholar
  109. 109.
    Widera, D., Grimm, W. D., Moebius, J. M., et al. (2007). Highly efficient neural differentiation of human somatic stem cells, isolated by minimally invasive periodontal surgery. Stem Cells and Development, 16, 447–460.PubMedGoogle Scholar
  110. 110.
    Osathanon, T., Manokawinchoke, J., Nowwarote, N., Aguilar, P., Palaga, T., & Pavasant, P. (2013). Notch signaling is involved in neurogenic commitment of human periodontal ligament-derived mesenchymal stem cells. Stem Cells and Development, 22, 1220–1231.PubMedCentralPubMedGoogle Scholar
  111. 111.
    Huang, L., Liang, J., Geng, Y., et al. (2013). Directing adult human periodontal ligament-derived stem cells to retinal fate. Investigative Ophthalmology & Visual Science, 54, 3965–3974.Google Scholar
  112. 112.
    Lee, J. H., Um, S., Song, I. S., Kim, H. Y., & Seo, B. M. (2014). Neurogenic differentiation of human dental stem cells in vitro. Journal Korean Association Oral Maxillofacial Surgery, 40, 173–180.Google Scholar
  113. 113.
    Kato, H., Taguchi, Y., Tominaga, K., Umeda, M., & Tanaka, A. (2014). Porphyromonas gingivalis LPS inhibits osteoblastic differentiation and promotes pro-inflammatory cytokine production in human periodontal ligament stem cells. Archives of Oral Biology, 59, 167–175.PubMedGoogle Scholar
  114. 114.
    Paik, Y. H., Schwabe, R. F., Bataller, R., Russo, M. P., Jobin, C., & Brenner, D. A. (2003). Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology, 37, 1043–1055.PubMedGoogle Scholar
  115. 115.
    Wang, X. B., Chen, X., Song, K. D., et al. (2010). Effects of HMGB1 on human cord blood CD34(+) hematopoietic stem cells proliferation and differentiation in vitro. Zhonghua Xue Ye Xue Za Zhi, 31, 88–91.PubMedGoogle Scholar
  116. 116.
    Monzen, S., Yoshino, H., Kasai-Eguchi, K., & Kashiwakura, I. (2013). Characteristics of myeloid differentiation and maturation pathway derived from human hematopoietic stem cells exposed to different linear energy transfer radiation types. PloS One, 8, e59385.PubMedCentralPubMedGoogle Scholar
  117. 117.
    Levin, S., Pevsner-Fischer, M., Kagan, S., et al. (2014). Divergent levels of LBP and TGFbeta1 in murine MSCs lead to heterogenic response to TLR and proinflammatory cytokine activation. Stem Cell Reviews, 10, 376–388.PubMedGoogle Scholar
  118. 118.
    Xu, J., Woods, C. R., Mora, A. L., et al. (2007). Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice. American Journal of Physiology - Lung Cellular and Molecular Physiology, 293, L131–L141.PubMedGoogle Scholar
  119. 119.
    Xu, S., De Becker, A., Van Camp, B., Vanderkerken, K., & Van Riet, I. (2010). An improved harvest and in vitro expansion protocol for murine bone marrow-derived mesenchymal stem cells. Journal of Biomedicine and Biotechnology, 2010, 105940.PubMedCentralPubMedGoogle Scholar
  120. 120.
    Huh, J. E., & Lee, S. Y. (1833). IL-6 is produced by adipose-derived stromal cells and promotes osteogenesis. Biochimica et Biophysica Acta, 2013, 2608–2616.Google Scholar
  121. 121.
    Secunda, R., Vennila, R., Mohanashankar, A. M., Rajasundari, M., Jeswanth, S., Surendran, R. (2014). Isolation, expansion and characterisation of mesenchymal stem cells from human bone marrow, adipose tissue, umbilical cord blood and matrix: a comparative study. Cytotechnology. doi: 10.1007/s10616-014-9718-z.
  122. 122.
    Al-Nbaheen, M., Vishnubalaji, R., Ali, D., et al. (2013). Human stromal (mesenchymal) stem cells from bone marrow, adipose tissue and skin exhibit differences in molecular phenotype and differentiation potential. Stem Cell Reviews, 9, 32–43.PubMedCentralPubMedGoogle Scholar
  123. 123.
    Raicevic, G., Najar, M., Stamatopoulos, B., et al. (2011). The source of human mesenchymal stromal cells influences their TLR profile as well as their functional properties. Cellular Immunology, 270, 207–216.PubMedGoogle Scholar
  124. 124.
    Khoury, J., & Langleben, D. (1998). Effects of endotoxin on lung pericytes in vitro. Microvascular Research, 56, 71–84.PubMedGoogle Scholar
  125. 125.
    Lindemann, D., Werle, S. B., Steffens, D., Garcia-Godoy, F., Pranke, P., & Casagrande, L. (2014). Effects of cryopreservation on the characteristics of dental pulp stem cells of intact deciduous teeth. Archives of Oral Biology, 59, 970–976.PubMedGoogle Scholar
  126. 126.
    Sudchada, S., & Kheolamai, P. (2012). Y UP, et al. CD14−/CD34+ is the founding population of umbilical cord blood-derived endothelial progenitor cells and angiogenin1 is an important factor promoting the colony formation. Annals of Hematology, 91, 321–329.PubMedGoogle Scholar
  127. 127.
    Waterman, R. S., Tomchuck, S. L., Henkle, S. L., & Betancourt, A. M. (2010). A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PloS One, 5, e10088.PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Reading School of PharmacyUniversity of ReadingReadingUnited Kingdom
  2. 2.Institute of Transfusion Medicine and Immunology, Medical Faculty MannheimHeidelberg UniversityHeidelbergGermany

Personalised recommendations