Abstract
It is becoming increasingly evident that inflammatory reactions of microglia contribute to the pathology of neurodegenerative diseases. Although the focus for rescuing neurones previously lied on minimising direct insult (including limiting aggregation of misfolded proteins and antagonising the effects of glutamate), therapeutic approaches now include moderating the ensuing inflammatory responses of microglia. Microglia responses in the central nervous system (CNS) are diverse and their involvement in both neuroprotection and neurotoxicity may seem paradoxical. Accordingly, management of neuroinflammation must include an understanding of conditions that trigger neurotoxic responses by microglia and deciphering strategies to maintain their neuroprotective phenotype. Mesenchymal stem cells (MSC) are stem cells with great capacity for immunomodulation on a wide range of immune cells. Evidence presented here highlights the potential of using MSC to modulate the inflammatory responses of microglia. The mechanisms underlying the ability of MSC to moderate microglia responses are also explained in this review. Although many aspects of this approach will require defined characterisation, MSC serve as a potential cell-based therapy that may slow or halt the progression of inflammatory CNS diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822
Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42–48
Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57–69
Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V, Uccelli A (2006) Human mesenchymal stem cells modulate B-cell functions. Blood 107:367–372
Coyne TM, Marcus AJ, Woodbury D, Black IB (2006) Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia. Stem Cells 24:2483–2492
Gao HM, Liu B, Zhang W, Hong JS (2003) Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J 17:1954–1956
Gibbons HM, Dragunow M (2006) Microglia induce neural cell death via a proximity-dependent mechanism involving nitric oxide. Brain Res 1084:1–15
Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845
Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F (2005) Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 105:2821–2827
Graeber MB (2010) Changing face of microglia. Science 330:783–788
Groh ME, Maitra B, Szekely E, Koc ON (2005) Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol 33:928–934
Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394
Jana M, Liu X, Koka S, Ghosh S, Petro TM, Pahan K (2001) Ligation of CD40 stimulates the induction of nitric-oxide synthase in microglial cells. J Biol Chem 276:44527–44533
Kim J, Hematti P (2009) Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hematol 37:1445–1453
Kitamura Y, Takata K, Inden M, Tsuchiya D, Yanagisawa D, Nakata J, Taniguchi T (2004) Intracerebroventricular injection of microglia protects against focal brain ischemia. J Pharmacol Sci 94:203–206
Lalancette-Hebert M, Gowing G, Simard A, Weng YC, Kriz J (2007) Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. J Neurosci 27:2596–2605
Lee JK, Jin HK, Endo S, Schuchman EH, Carter JE, Bae JS (2010) Intracerebral transplantation of bone marrow-derived mesenchymal stem cells reduces amyloid-beta deposition and rescues memory deficits in Alzheimer’s disease mice by modulation of immune responses. Stem Cells 28:329–343
Lv M, Liu Y, Zhang J, Sun L, Liu Z, Zhang S, Wang B, Su D, Su Z (2011) Roles of inflammation response in microglia cell through Toll-like receptors 2/interleukin-23/interleukin-17 pathway in cerebral ischemia/reperfusion injury. Neuroscience 176:162–172
Mantovani A, Sica A, Locati M (2005) Macrophage polarization comes of age. Immunity 23:344–346
Muller I, Lymperi S, Dazzi F (2008) Mesenchymal stem cell therapy for degenerative inflammatory disorders. Curr Opin Organ Transplant 13:639–644
Munoz JR, Stoutenger BR, Robinson AP, Spees JL, Prockop DJ (2005) Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice. Proc Natl Acad Sci USA 102:18171–18176
Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318
Ooi YY, Ramasamy R, Rahmat Z, Subramaiam H, Tan SW, Abdullah M, Israf DA, Vidyadaran S (2010) Bone marrow-derived mesenchymal stem cells modulate BV2 microglia responses to lipopolysaccharide. Int Immunopharmacol 10:1532–1540
Ponomarev ED, Shriver LP, Dittel BN (2006) CD40 expression by microglial cells is required for their completion of a two-step activation process during central nervous system autoimmune inflammation. J Immunol 176:1402–1410
Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB (2010) Pro-inflammatory cytokines, IFNgamma and TNFalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PLoS One 5:e9016
Raffaghello L, Bianchi G, Bertolotto M, Montecucco F, Busca A, Dallegri F, Ottonello L, Pistoia V (2008) Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem Cells 26:151–162
Ramasamy R, Fazekasova H, Lam EW, Soeiro I, Lombardi G, Dazzi F (2007) Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle. Transplantation 83:71–76
Ransohoff RM, Cardona AE (2010) The myeloid cells of the central nervous system parenchyma. Nature 468:253–262
Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y (2008) Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2:141–150
Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, Muroi K, Ozawa K (2007) Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 109:228–234
Sheikh AM, Nagai A, Wakabayashi K, Narantuya D, Kobayashi S, Yamaguchi S, Kim SU (2011) Mesenchymal stem cell transplantation modulates neuroinflammation in focal cerebral ischemia: contribution of fractalkine and IL-5. Neurobiol Dis 41:717–724
Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L (2008) Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 111:1327–1333
Takata K, Kitamura Y, Yanagisawa D, Morikawa S, Morita M, Inubushi T, Tsuchiya D, Chishiro S, Saeki M, Taniguchi T, Shimohama S, Tooyama I (2007) Microglial transplantation increases amyloid-beta clearance in Alzheimer model rats. FEBS Lett 581:475–478
Uccelli A, Moretta L, Pistoia V (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8:726–736
Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi DK, Ischiropoulos H, Przedborski S (2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 22:1763–1771
Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, Giunti D, Ceravolo A, Cazzanti F, Frassoni F, Mancardi G, Uccelli A (2005) Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood 106:1755–1761
Zhou C, Zhang C, Chi S, Xu Y, Teng J, Wang H, Song Y, Zhao R (2009) Effects of human marrow stromal cells on activation of microglial cells and production of inflammatory factors induced by lipopolysaccharide. Brain Res 1269:23–30
Acknowledgements
The authors would like to acknowledge funding from the Research University Grant Scheme (04-02-10-0924RU, 04-01-07-0113RU and 04-01-09-0781RU) for their support and Ms. Shiyamala Subramaniam for assistance with the artwork.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Vidyadaran, S., Ramasamy, R., Seow, H.F. (2012). Immunomodulatory Potential of Mesenchymal Stem Cells on Microglia. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 6. Stem Cells and Cancer Stem Cells, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2993-3_22
Download citation
DOI: https://doi.org/10.1007/978-94-007-2993-3_22
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-2992-6
Online ISBN: 978-94-007-2993-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)