Tackling the physiological barriers for successful mesenchymal stem cell transplantation into the central nervous system

Stem Cell Research and Therapy

Volumn 4, Issue 4, 2013, Pages

  De Vocht, Nathalie ^a   Praet, Jelle ^a   Reekmans, Kristien ^a   Le Blon, Debbie ^a   Hoornaert, Chloé ^a   Daans, Jasmijn ^a   Berneman, Zwi ^a   Van Der Linden, Annemie ^a   Ponsaerts, Peter ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

CD200 ANTIGEN; CD200 RECEPTOR; CHEMOKINE RECEPTOR CX3CR1; FRACTALKINE; GROWTH FACTOR;

CELL ACTIVATION; CELL DEATH; CELL HYPOXIA; CELL SURVIVAL; CLINICAL EFFECTIVENESS; DEGENERATIVE DISEASE; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; IN VITRO STUDY; IN VIVO STUDY; MESENCHYMAL STEM CELL TRANSPLANTATION; MICROGLIA; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN SECRETION; REVIEW; CENTRAL NERVOUS SYSTEM; MESENCHYMAL STROMA CELL; PATHOLOGY; PHYSIOLOGY; PROCEDURES;

CENTRAL NERVOUS SYSTEM; HUMANS; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS;

EID: 84887855819     PISSN: None     EISSN: 17576512     Source Type: Journal    
DOI: 10.1186/scrt312     Document Type: Review

References (143)

1. Mesenchymal stem cells as therapeutic agents and potential targeted gene delivery vehicle for brain diseases. Huang B, Tabata Y, Gao JQ, J Control Release 2012 162 464 473 22885026
2. Mesenchymal stem cells for the treatment of neurodegenerative disease. Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA, Regen Med 2010 5 933 946 21082892
3. Stem cells: an overview of the current status of therapies for central and peripheral nervous system diseases. Orlacchio A, Bernardi G, Martino S, Curr Med Chem 2010 17 595 608 20088765
4. Neuroprotective features of mesenchymal stem cells. Uccelli A, Benvenuto F, Laroni A, Giunti D, Best Pract Res Clin Haematol 2011 24 59 64 21396593
5. Autotransplantation of bone marrow-derived stem cells as a therapy for neurodegenerative diseases. Kan I, Melamed E, Offen D, Handb Exp Pharmacol 2007 180 219 242 17554511
6. Mesenchymal stem cells enhance the engraftment and myelinating ability of allogeneic oligodendrocyte progenitors in dysmyelinated mice. Cristofanilli M, Harris VK, Zigelbaum A, Goossens AM, Lu A, Rosenthal H, Sadiq SA, Stem Cells Dev 2011 20 2065 2076 21299379
7. Transplantation of placenta-derived mesenchymal stem cells in the EAE mouse model of MS. Fisher-Shoval Y, Barhum Y, Sadan O, Yust-Katz S, Ben-Zur T, Lev N, Benkler C, Hod M, Melamed E, Offen D, J Mol Neurosci 2012 48 176 184 22638856
8. Bone marrow mesenchymal stem cells can improve the motor function of a Huntington's disease rat model. Jiang Y, Lv H, Huang S, Tan H, Zhang Y, Li H, Neurol Res 2011 33 331 337 21513650
9. Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease: morphological and behavioral outcomes. Rossignol J, Boyer C, Leveque X, Fink KD, Thinard R, Blanchard F, Dunbar GL, Lescaudron L, Behav Brain Res 2011 217 369 378 21070819
10. Systemically administered human bone marrow-derived mesenchymal stem home into peripheral organs but do not induce neuroprotective effects in the MCAo-mouse model for cerebral ischemia. Steiner B, Roch M, Holtkamp N, Kurtz A, Neurosci Lett 2012 513 25 30 22342911
11. Intracerebral transplantation of mesenchymal stem cells derived from human umbilical cord blood alleviates hypoxic ischemic brain injury in rat neonates. Xia G, Hong X, Chen X, Lan F, Zhang G, Liao L, J Perinat Med 2010 38 215 221 20121545
12. Neuroprotective effect of human mesenchymal stem cells in an animal model of double toxin-induced multiple system atrophy parkinsonism. Park HJ, Bang G, Lee BR, Kim HO, Lee PH, Cell Transplant 2011 20 827 835 21054946
13. Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: a potential therapy for Huntington's disease. Sadan O, Shemesh N, Barzilay R, Dadon-Nahum M, Blumenfeld-Katzir T, Assaf Y, Yeshurun M, Djaldetti R, Cohen Y, Melamed E, Offen D, Exp Neurol 2012 234 417 427 22285250
14. Development of a middle cerebral artery occlusion model in the nonhuman primate and a safety study of i.v. infusion of human mesenchymal stem cells. Sasaki M, Honmou O, Radtke C, Kocsis JD, PLoS One 2011 6 26577 22039510
15. NT-3-secreting human umbilical cord mesenchymal stromal cell transplantation for the treatment of acute spinal cord injury in rats. Shang AJ, Hong SQ, Xu Q, Wang HY, Yang Y, Wang ZF, Xu BN, Jiang XD, Xu RX, Brain Res 2011 1391 102 113 21420392
16. Direct intrathecal implantation of mesenchymal stromal cells leads to enhanced neuroprotection via an NFkappaB-mediated increase in interleukin-6 production. Walker PA, Harting MT, Jimenez F, Shah SK, Pati S, Dash PK, Cox CS Jr, Stem Cells Dev 2010 19 867 876 19775197
17. Intravenous administration of 99mTc-HMPAO-labeled human mesenchymal stem cells after stroke: in vivo imaging and biodistribution. Detante O, Moisan A, Dimastromatteo J, Richard MJ, Riou L, Grillon E, Barbier E, Desruet MD, De Fraipont F, Segebarth C, Jaillard A, Hommel M, Ghezzi C, Remy C, Cell Transplant 2009 18 1369 1379 19849895
18. Clinical potential of intravenous neural stem cell delivery for treatment of neuroinflammatory disease in mice? Reekmans KP, Praet J, De Vocht N, Tambuyzer BR, Bergwerf I, Daans J, Baekelandt V, Vanhoutte G, Goossens H, Jorens PG, Ysebaert DK, Chatterjee S, Pauwels P, Van Marck E, Berneman ZN, Van der Linden A, Ponsaerts P, Cell Transplant 2011 20 851 869 21092405
19. Limitations of intravenous human bone marrow CD133+ cell grafts in stroke rats. Borlongan CV, Evans A, Yu G, Hess DC, Brain Res 2005 1048 116 122 15921661 (Pubitemid 40800265)
20. Labeling of Luciferase/eGFP-expressing bone marrow-derived stromal cells with fluorescent micron-sized iron oxide particles improves quantitative and qualitative multimodal imaging of cellular grafts in vivo. De Vocht N, Bergwerf I, Vanhoutte G, Daans J, De Visscher G, Chatterjee S, Pauwels P, Berneman Z, Ponsaerts P, Van der Linden A, Mol Imaging Biol 2011 13 1133 1145 21246293
21. Quantitative and phenotypic analysis of mesenchymal stromal cell graft survival and recognition by microglia and astrocytes in mouse brain. De Vocht N, Lin D, Praet J, Hoornaert C, Reekmans K, Le Blon D, Daans J, Pauwels P, Goossens H, Hens N, Berneman Z, Van der Linden A, Ponsaerts P, Immunobiology 2012 218 696 705 22944251
22. Transplantation of neuronal-primed human bone marrow mesenchymal stem cells in hemiparkinsonian rodents. Khoo ML, Tao H, Meedeniya AC, Mackay-Sim A, Ma DD, PLoS One 2011 6 19025 21625433
23. Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer's disease mouse model through modulation of neuroinflammation. Lee HJ, Lee JK, Lee H, Carter JE, Chang JW, Oh W, Yang YS, Suh JG, Lee BH, Jin HK, Bae JS, Neurobiol Aging 2012 33 588 602 20471717
24. 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. Lee JK, Jin HK, Endo S, Schuchman EH, Carter JE, Bae JS, Stem Cells 2010 28 329 343 20014009
25. Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury. Nakajima H, Uchida K, Guerrero AR, Watanabe S, Sugita D, Takeura N, Yoshida A, Long G, Wright KT, Johnson WE, Baba H, J Neurotrauma 2012 29 1614 1625 22233298
26. Potential of rat bone marrow-derived mesenchymal stem cells as vehicles for delivery of neurotrophins to the Parkinsonian rat brain. Moloney TC, Rooney GE, Barry FP, Howard L, Dowd E, Brain Res 2010 1359 33 43 20732313
27. Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. Zhang M, Methot D, Poppa V, Fujio Y, Walsh K, Murry CE, J Mol Cell Cardiol 2001 33 907 921 11343414 (Pubitemid 32545326)
28. Pathogen recognition and innate immunity. Akira S, Uematsu S, Takeuchi O, Cell 2006 124 783 801 16497588 (Pubitemid 43261452)
29. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Block ML, Zecca L, Hong JS, Nat Rev Neurosci 2007 8 57 69 17180163 (Pubitemid 46011999)
30. Toll-like receptors: roles in neuroprotection? Hanisch UK, Johnson TV, Kipnis J, Trends Neurosci 2008 31 176 182 18329736
31. Toll-like receptors and innate immunity. Uematsu S, Akira S, J Mol Med (Berl) 2006 84 712 725 16924467 (Pubitemid 44328063)
32. Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Hanke ML, Kielian T, Clin Sci (Lond) 2011 121 367 387 21745188
33. Allogeneic stromal cell implantation in brain tissue leads to robust microglial activation. Tambuyzer BR, Bergwerf I, De Vocht N, Reekmans K, Daans J, Jorens PG, Goossens H, Ysebaert DK, Chatterjee S, Van Marck E, Berneman ZN, Ponsaerts P, Immunol Cell Biol 2009 87 267 273 19290016
34. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. Olson JK, Miller SD, J Immunol 2004 173 3916 3924 15356140 (Pubitemid 39280755)
35. Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Lehnardt S, Glia 2010 58 253 263 19705460
36. Reanalysis of P2X7 receptor expression in rodent brain. Sim JA, Young MT, Sung HY, North RA, Surprenant A, J Neurosci 2004 24 6307 6314 15254086 (Pubitemid 38944221)
37. The P2X7 purinergic receptor: from physiology to neurological disorders. Skaper SD, Debetto P, Giusti P, FASEB J 2010 24 337 345 19812374
38. Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation. Qin L, Li G, Qian X, Liu Y, Wu X, Liu B, Hong JS, Block ML, Glia 2005 52 78 84 15920727 (Pubitemid 41532140)
39. Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation. Hu X, Chen J, Wang L, Ivashkiv LB, J Leukoc Biol 2007 82 237 243 17502339 (Pubitemid 47230632)
40. Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression. Kotter MR, Zhao C, van Rooijen N, Franklin RJ, Neurobiol Dis 2005 18 166 175 15649707 (Pubitemid 40092906)
41. Complement-receptor-3 and scavenger-receptor-AI/II mediated myelin phagocytosis in microglia and macrophages. Reichert F, Rotshenker S, Neurobiol Dis 2003 12 65 72 12609490
42. Alternative activation of macrophages: an immunologic functional perspective. Martinez FO, Helming L, Gordon S, Annu Rev Immunol 2009 27 451 483 19105661
43. Integration of metabolism and inflammation by lipid-activated nuclear receptors. Bensinger SJ, Tontonoz P, Nature 2008 454 470 477 18650918
44. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG, J Neurosci 2009 29 13435 13444 19864556
45. Alternative activation of macrophages. Gordon S, Nat Rev Immunol 2003 3 23 35 12511873 (Pubitemid 37328697)
46. Monocyte and macrophage heterogeneity. Gordon S, Taylor PR, Nat Rev Immunol 2005 5 953 964 16322748 (Pubitemid 41746764)
47. The brain tumor microenvironment. Charles NA, Holland EC, Gilbertson R, Glass R, Kettenmann H, Glia 2011 59 1169 1180 21446047
48. Immunity, inflammation, and cancer. Grivennikov SI, Greten FR, Karin M, Cell 2010 140 883 899 20303878
49. Microglial cell origin and phenotypes in health and disease. Saijo K, Glass CK, Nat Rev Immunol 2011 11 775 787 22025055
50. Heterogeneity of microglial activation in the innate immune response in the brain. Colton CA, J Neuroimmune Pharmacol 2009 4 399 418 19655259
51. Reporter gene-expressing bone marrow-derived stromal cells are immune-tolerated following implantation in the central nervous system of syngeneic immunocompetent mice. Bergwerf I, De Vocht N, Tambuyzer B, Verschueren J, Reekmans K, Daans J, Ibrahimi A, Van Tendeloo V, Chatterjee S, Goossens H, Jorens PG, Baekelandt V, Ysebaert D, Van Marck E, Berneman ZN, Linden AV, Ponsaerts P, BMC Biotechnol 2009 9 1 19128466
52. Cell type-associated differences in migration, survival and immunogenicity following grafting in CNS tissue. Praet J, Reekmans K, Lin D, De Vocht N, Bergwerf I, Tambuyzer B, Daans J, Hens N, Goossens H, Pauwels P, Berneman Z, Van der Linden A, Ponsaerts P, Cell Transplant 2012 21 1867 1881 22472278
53. Disparate host response and donor survival after the transplantation of mesenchymal or neuroectodermal cells to the intact rodent brain. Coyne TM, Marcus AJ, Reynolds K, Black IB, Woodbury D, Transplantation 2007 84 1507 1516 18091528 (Pubitemid 350294727)
54. The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease. Lee HJ, Lee JK, Lee H, Shin JW, Carter JE, Sakamoto T, Jin HK, Bae JS, Neurosci Lett 2010 481 30 35 20600610
55. Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton's jelly, and umbilical cord blood for treating spinal cord injuries in dogs. Ryu HH, Kang BJ, Park SS, Kim Y, Sung GJ, Woo HM, Kim WH, Kweon OK, J Vet Med Sci 2012 74 1617 1630 22878503
56. Mesenchymal stem cell transplantation modulates neuroinflammation in focal cerebral ischemia: contribution of fractalkine and IL-5. Sheikh AM, Nagai A, Wakabayashi K, Narantuya D, Kobayashi S, Yamaguchi S, Kim SU, Neurobiol Dis 2011 41 717 724 21168500
57. Bone marrow mesenchymal stem cells in a three dimensional gelatin sponge scaffold attenuate inflammation, promote angiogenesis and reduce cavity formation in experimental spinal cord injury. Zeng X, Zeng YS, Ma YH, Lu LY, Du BL, Zhang W, Li Y, Chan WY, Cell Transplant 2011 20 1881 1899 21396163
58. The yin and yang of microglia. Czeh M, Gressens P, Kaindl AM, Dev Neurosci 2011 33 199 209 21757877
59. Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Thored P, Heldmann U, Gomes-Leal W, Gisler R, Darsalia V, Taneera J, Nygren JM, Jacobsen SE, Ekdahl CT, Kokaia Z, Lindvall O, Glia 2009 57 835 849 19053043
60. Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS. Liao B, Zhao W, Beers DR, Henkel JS, Appel SH, Exp Neurol 2012 237 147 152 22735487
61. Immunomodulatory properties of mesenchymal stromal cells. Nauta AJ, Fibbe WE, Blood 2007 110 3499 3506 17664353 (Pubitemid 350159613)
62. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Nimmerjahn A, Kirchhoff F, Helmchen F, Science 2005 308 1314 1318 15831717 (Pubitemid 40746128)
63. Fractalkine and fractalkine receptors in human neurons and glial cells. Hatori K, Nagai A, Heisel R, Ryu JK, Kim SU, J Neurosci Res 2002 69 418 426 12125082 (Pubitemid 34809490)
64. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O, Cell 1997 91 521 530 9390561 (Pubitemid 27508241)
65. Fractalkine mediates communication between pathogenic proteins and microglia: implications of anti-inflammatory treatments in different stages of neurodegenerative diseases. Desforges NM, Hebron ML, Algarzae NK, Lonskaya I, Moussa CE, Int J Alzheimers Dis 2012 2012 345472 22919540
66. Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system. Tong N, Perry SW, Zhang Q, James HJ, Guo H, Brooks A, Bal H, Kinnear SA, Fine S, Epstein LG, Dairaghi D, Schall TJ, Gendelman HE, Dewhurst S, Sharer LR, Gelbard HA, J Immunol 2000 164 1333 1339 10640747 (Pubitemid 30067246)
67. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Fuhrmann M, Bittner T, Jung CK, Burgold S, Page RM, Mitteregger G, Haass C, LaFerla FM, Kretzschmar H, Herms J, Nat Neurosci 2010 13 411 413 20305648
68. CX3CR1 deficiency alters microglial activation and reduces beta-amyloid deposition in two Alzheimer's disease mouse models. Lee S, Varvel NH, Konerth ME, Xu G, Cardona AE, Ransohoff RM, Lamb BT, Am J Pathol 2010 177 2549 2562 20864679
69. Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse. Denes A, Ferenczi S, Halasz J, Kornyei Z, Kovacs KJ, J Cereb Blood Flow Metab 2008 28 1707 1721 18575457
70. CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar amyloid-beta phagocytosis. Liu Z, Condello C, Schain A, Harb R, Grutzendler J, J Neurosci 2010 30 17091 17101 21159979
71. Control of microglial neurotoxicity by the fractalkine receptor. Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S, Lira SA, Littman DR, Ransohoff RM, Nat Neurosci 2006 9 917 924 16732273 (Pubitemid 43980506)
72. The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system. Huang D, Shi FD, Jung S, Pien GC, Wang J, Salazar-Mather TP, He TT, Weaver JT, Ljunggren HG, Biron CA, Littman DR, Ransohoff RM, FASEB J 2006 20 896 905 16675847 (Pubitemid 44943947)
73. CX3CR1 protein signaling modulates microglial activation and protects against plaque-independent cognitive deficits in a mouse model of Alzheimer disease. Cho SH, Sun B, Zhou Y, Kauppinen TM, Halabisky B, Wes P, Ransohoff RM, Gan L, J Biol Chem 2011 286 32713 32722 21771791
74. CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity. Rogers JT, Morganti JM, Bachstetter AD, Hudson CE, Peters MM, Grimmig BA, Weeber EJ, Bickford PC, Gemma C, J Neurosci 2011 31 16241 16250 22072675
75. Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS. Hughes PM, Botham MS, Frentzel S, Mir A, Perry VH, Glia 2002 37 314 327 11870871
76. An engineered CX3CR1 antagonist endowed with anti-inflammatory activity. Dorgham K, Ghadiri A, Hermand P, Rodero M, Poupel L, Iga M, Hartley O, Gorochov G, Combadiere C, Deterre P, J Leukoc Biol 2009 86 903 911 19571253
77. Mesenchymal stem cells shape microglia effector functions through the release of CX3CL1. Giunti D, Parodi B, Usai C, Vergani L, Casazza S, Bruzzone S, Mancardi G, Uccelli A, Stem Cells 2012 30 2044 2053 22821677
78. The myeloid cells of the central nervous system parenchyma. Ransohoff RM, Cardona AE, Nature 2010 468 253 262 21068834
79. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM, Blom B, Homola ME, Streit WJ, Brown MH, Barclay AN, Sedgwick JD, Science 2000 290 1768 1771 11099416 (Pubitemid 32004808)
80. CD200 ligand receptor interaction modulates microglial activation in vivo and in vitro: a role for IL-4. Lyons A, Downer EJ, Crotty S, Nolan YM, Mills KH, Lynch MA, J Neurosci 2007 27 8309 8313 17670977 (Pubitemid 47219605)
81. Regulation of microglial cell responses in murine Toxoplasma encephalitis by CD200/CD200 receptor interaction. Deckert M, Sedgwick JD, Fischer E, Schluter D, Acta Neuropathol 2006 111 548 558 16718351 (Pubitemid 43778959)
82. Elevated neuronal expression of CD200 protects Wlds mice from inflammation-mediated neurodegeneration. Chitnis T, Imitola J, Wang Y, Elyaman W, Chawla P, Sharuk M, Raddassi K, Bronson RT, Khoury SJ, Am J Pathol 2007 170 1695 1712 17456775 (Pubitemid 47339314)
83. Microglia: gatekeepers of central nervous system immunology. Tambuyzer BR, Ponsaerts P, Nouwen EJ, J Leukoc Biol 2009 85 352 370 19028958
84. Decreased neuronal CD200 expression in IL-4-deficient mice results in increased neuroinflammation in response to lipopolysaccharide. Lyons A, McQuillan K, Deighan BF, O'Reilly JA, Downer EJ, Murphy AC, Watson M, Piazza A, O'Connell F, Griffin R, Mills KH, Lynch MA, Brain Behav Immun 2009 23 1020 1027 19501645
85. Expression of CD200 in alternative activation of microglia following an excitotoxic lesion in the mouse hippocampus. Yi MH, Zhang E, Kang JW, Shin YN, Byun JY, Oh SH, Seo JH, Lee YH, Kim DW, Brain Res 2012 1481 90 96 22975132
86. Decreased expression of CD200 and CD200 receptor in Alzheimer's disease: a potential mechanism leading to chronic inflammation. Walker DG, Dalsing-Hernandez JE, Campbell NA, Lue LF, Exp Neurol 2009 215 5 19 18938162
87. Monoclonal antibody-mediated CD200 receptor signaling suppresses macrophage activation and tissue damage in experimental autoimmune uveoretinitis. Copland DA, Calder CJ, Raveney BJ, Nicholson LB, Phillips J, Cherwinski H, Jenmalm M, Sedgwick JD, Dick AD, Am J Pathol 2007 171 580 588 17600119 (Pubitemid 47344690)
88. CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson's disease. Zhang S, Wang XJ, Tian LP, Pan J, Lu GQ, Zhang YJ, Ding JQ, Chen SD, J Neuroinflammation 2011 8 154 22053982
89. CD200 positive human mesenchymal stem cells suppress TNF-alpha secretion from CD200 receptor positive macrophage-like cells. Pietila M, Lehtonen S, Tuovinen E, Lahteenmaki K, Laitinen S, Leskela HV, Natynki A, Pesala J, Nordstrom K, Lehenkari P, PLoS One 2012 7 31671 22363701
90. Mesenchymal stem cells as trophic mediators. Caplan AI, Dennis JE, J Cell Biochem 2006 98 1076 1084 16619257 (Pubitemid 44128350)
91. Bone marrow-derived mesenchymal stem cells modulate BV2 microglia responses to lipopolysaccharide. Ooi YY, Ramasamy R, Rahmat Z, Subramaiam H, Tan SW, Abdullah M, Israf DA, Vidyadaran S, Int Immunopharmacol 2010 10 1532 1540 20850581
92. Effects of human marrow stromal cells on activation of microglial cells and production of inflammatory factors induced by lipopolysaccharide. Zhou C, Zhang C, Chi S, Xu Y, Teng J, Wang H, Song Y, Zhao R, Brain Res 2009 1269 23 30 19269277
93. Immunomodulatory influence of bone marrow-derived mesenchymal stem cells on neuroinflammation in astrocyte cultures. Schafer S, Calas AG, Vergouts M, Hermans E, J Neuroimmunol 2012 249 40 48 22633273
94. Soluble CCL5 derived from bone marrow-derived mesenchymal stem cells and activated by amyloid beta ameliorates Alzheimer's disease in mice by recruiting bone marrow-induced microglia immune responses. Lee JK, Schuchman EH, Jin HK, Bae JS, Stem Cells 2012 30 1544 1555 22570192
95. Early intervention with gene-modified mesenchymal stem cells overexpressing interleukin-4 enhances anti-inflammatory responses and functional recovery in experimental autoimmune demyelination. Payne NL, Dantanarayana A, Sun G, Moussa L, Caine S, McDonald C, Herszfeld D, Bernard CC, Siatskas C, Cell Adh Migr 2012 6 179 189 22568986
96. Immunologically privileged sites. Barker CF, Billingham RE, Adv Immunol 1977 25 1 54 345773
97. CNS immune privilege: hiding in plain sight. Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC, Immunol Rev 2006 213 48 65 16972896 (Pubitemid 44401493)
98. Recognition of cellular implants by the brain's innate immune system. Bergwerf I, Tambuyzer B, De Vocht N, Reekmans K, Praet J, Daans J, Chatterjee S, Pauwels P, Van der Linden A, Berneman ZN, Ponsaerts P, Immunol Cell Biol 2011 89 511 516 21102538
99. Current challenges for the advancement of neural stem cell biology and transplantation research. Reekmans K, Praet J, Daans J, Reumers V, Pauwels P, Van der Linden A, Berneman ZN, Ponsaerts P, Stem Cell Rev 2012 8 262 278 21537994
100. Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells. Zhu W, Chen J, Cong X, Hu S, Chen X, Stem Cells 2006 24 416 425 16253984 (Pubitemid 44464811)
101. Transplantation of Flk-1+ human bone marrow-derived mesenchymal stem cells promotes angiogenesis and neurogenesis after cerebral ischemia in rats. Bao X, Feng M, Wei J, Han Q, Zhao H, Li G, Zhu Z, Xing H, An Y, Qin C, Zhao RC, Wang R, Eur J Neurosci 2011 34 87 98 21692879
102. Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats. Bao X, Wei J, Feng M, Lu S, Li G, Dou W, Ma W, Ma S, An Y, Qin C, Zhao RC, Wang R, Brain Res 2011 1367 103 113 20977892
103. Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia. Zheng W, Honmou O, Miyata K, Harada K, Suzuki J, Liu H, Houkin K, Hamada H, Kocsis JD, Brain Res 2010 1310 8 16 19913518
104. Genetically engineered mesenchymal stem cells reduce behavioral deficits in the YAC 128 mouse model of Huntington's disease. Dey ND, Bombard MC, Roland BP, Davidson S, Lu M, Rossignol J, Sandstrom MI, Skeel RL, Lescaudron L, Dunbar GL, Behav Brain Res 2010 214 193 200 20493905
105. Transplantation of undifferentiated human mesenchymal stem cells protects against 6-hydroxydopamine neurotoxicity in the rat. Blandini F, Cova L, Armentero MT, Zennaro E, Levandis G, Bossolasco P, Calzarossa C, Mellone M, Giuseppe B, Deliliers GL, Polli E, Nappi G, Silani V, Cell Transplant 2010 19 203 217 19906332
106. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease. Danielyan L, Schafer R, von Ameln-Mayerhofer A, Bernhard F, Verleysdonk S, Buadze M, Lourhmati A, Klopfer T, Schaumann F, Schmid B, Koehle C, Proksch B, Weissert R, Reichardt HM, van den Brandt J, Buniatian GH, Schwab M, Gleiter CH, Frey WH 2nd, Rejuvenation Res 2011 14 3 16 21291297
107. Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells. Hu SL, Luo HS, Li JT, Xia YZ, Li L, Zhang LJ, Meng H, Cui GY, Chen Z, Wu N, Lin JK, Zhu G, Feng H, Crit Care Med 2010 38 2181 2189 20711072
108. Fate of transplanted bone marrow derived mesenchymal stem cells following spinal cord injury in rats by transplantation routes. Kang ES, Ha KY, Kim YH, J Korean Med Sci 2012 27 586 593 22690088
109. Comparison of transdifferentiated and untransdifferentiated human umbilical mesenchymal stem cells in rats after traumatic brain injury. Hong SQ, Zhang HT, You J, Zhang MY, Cai YQ, Jiang XD, Xu RX, Neurochem Res 2011 36 2391 2400 21877237
110. Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma. Zanier ER, Montinaro M, Vigano M, Villa P, Fumagalli S, Pischiutta F, Longhi L, Leoni ML, Rebulla P, Stocchetti N, Lazzari L, De Simoni MG, Crit Care Med 2011 39 2501 2510 21725237
111. Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells. Chacko SM, Ahmed S, Selvendiran K, Kuppusamy ML, Khan M, Kuppusamy P, Am J Physiol Cell Physiol 2010 299 1562 C1570 20861473
112. Surviving ischemia: adaptive responses mediated by hypoxia-inducible factor 1. Semenza GL, J Clin Invest 2000 106 809 812 11018065
113. Regulation of the chemokine receptor CXCR4 by hypoxia. Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, Bernasconi S, Saccani S, Nebuloni M, Vago L, Mantovani A, Melillo G, Sica A, J Exp Med 2003 198 1391 1402 14597738 (Pubitemid 37392484)
114. Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. Hung SC, Pochampally RR, Hsu SC, Sanchez C, Chen SC, Spees J, Prockop DJ, PLoS One 2007 2 416 17476338
115. Hypoxic preconditioning improves survival of cardiac progenitor cells: role of stromal cell derived factor-1alpha-CXCR4 axis. Yan F, Yao Y, Chen L, Li Y, Sheng Z, Ma G, PLoS One 2012 7 37948 22815687
116. The role of SDF-1-CXCR4/CXCR7 axis in the therapeutic effects of hypoxia-preconditioned mesenchymal stem cells for renal ischemia/reperfusion injury. Liu H, Liu S, Li Y, Wang X, Xue W, Ge G, Luo X, PLoS One 2012 7 34608 22511954
117. Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1alpha in MSCs. Liu H, Xue W, Ge G, Luo X, Li Y, Xiang H, Ding X, Tian P, Tian X, Biochem Biophys Res Commun 2010 401 509 515 20869949
118. Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. Hu X, Yu SP, Fraser JL, Lu Z, Ogle ME, Wang JA, Wei L, J Thorac Cardiovasc Surg 2008 135 799 808 18374759 (Pubitemid 351417929)
119. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Rosova I, Dao M, Capoccia B, Link D, Nolta JA, Stem Cells 2008 26 2173 2182 18511601
120. In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain. Theus MH, Wei L, Cui L, Francis K, Hu X, Keogh C, Yu SP, Exp Neurol 2008 210 656 670 18279854
121. Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats. Wei L, Fraser JL, Lu ZY, Hu X, Yu SP, Neurobiol Dis 2012 46 635 645 22426403
122. Erythropoietin improves the efficiency of endothelial progenitor cell therapy after myocardial infarction in mice: effects on transplanted cell survival and autologous endothelial progenitor cell mobilization. Cheng Y, Hu R, Lv L, Ling L, Jiang S, J Surg Res 2012 176 47 e55 22595018
123. Hypoxia-specific GM-CSF-overexpressing neural stem cells improve graft survival and functional recovery in spinal cord injury. Kim HJ, Oh JS, An SS, Pennant WA, Gwak SJ, Kim AN, Han PK, Yoon DH, Kim KN, Ha Y, Gene Ther 2012 19 513 521 22011644
124. Erythropoietin enhances cell proliferation and survival of human fetal neuronal progenitors in normoxia. Pavlica S, Milosevic J, Keller M, Schulze M, Peinemann F, Piscioneri A, De Bartolo L, Darsow K, Bartel S, Lange HA, Bader A, Brain Res 2012 1452 18 28 22444273
125. Hypoxia-inducible factor 1 alpha contributes to cardiac healing in mesenchymal stem cells-mediated cardiac repair. Cerrada I, Ruiz-Sauri A, Carrero R, Trigueros C, Dorronsoro A, Sanchez-Puelles JM, Diez-Juan A, Montero JA, Sepulveda P, Stem Cells Dev 2012 22 501 511 22873764
126. Neural stem cells modified by a hypoxia-inducible VEGF gene expression system improve cell viability under hypoxic conditions and spinal cord injury. Lian Jin H, Pennant WA, Hyung Lee M, Su S, Ah Kim H, Lu Liu M, Soo Oh J, Cho J, Nyun Kim K, Heum Yoon D, Ha Y, Spine (Phila Pa 1976) 2011 36 857 864 21192293
127. Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials. Pedraza E, Coronel MM, Fraker CA, Ricordi C, Stabler CL, Proc Natl Acad Sci USA 2012 109 4245 4250 22371586
128. An oxygen-permeable spheroid culture system for the prevention of central hypoxia and necrosis of spheroids. Anada T, Fukuda J, Sai Y, Suzuki O, Biomaterials 2012 33 8430 8441 22940219
129. Effects of transplantation with bone marrow-derived mesenchymal stem cells modified by Survivin on experimental stroke in rats. Liu N, Zhang Y, Fan L, Yuan M, Du H, Cheng R, Liu D, Lin F, J Transl Med 2011 9 105 21733181
130. Survival and immunogenicity of mesenchymal stem cells from the green fluorescent protein transgenic rat in the adult rat brain. Moloney TC, Dockery P, Windebank AJ, Barry FP, Howard L, Dowd E, Neurorehabil Neural Repair 2010 24 645 656 20378924
131. Improvement of deficits by transplantation of lentiviral vector-modified human amniotic mesenchymal cells after cerebral ischemia in rats. Tao J, Ji F, Liu B, Wang F, Dong F, Zhu Y, Brain Res 2012 1448 1 10 22386515
132. VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson's disease. Xiong N, Zhang Z, Huang J, Chen C, Jia M, Xiong J, Liu X, Wang F, Cao X, Liang Z, Sun S, Lin Z, Wang T, Gene Ther 2011 18 394 402 21107440
133. Minocycline-preconditioned neural stem cells enhance neuroprotection after ischemic stroke in rats. Sakata H, Niizuma K, Yoshioka H, Kim GS, Jung JE, Katsu M, Narasimhan P, Maier CM, Nishiyama Y, Chan PH, J Neurosci 2012 32 3462 3473 22399769
134. The therapeutic potential of human multipotent mesenchymal stromal cells combined with pharmacologically active microcarriers transplanted in hemi-parkinsonian rats. Delcroix GJ, Garbayo E, Sindji L, Thomas O, Vanpouille-Box C, Schiller PC, Montero-Menei CN, Biomaterials 2011 32 1560 1573 21074844
135. Human umbilical cord-derived Schwann-like cell transplantation combined with neurotrophin-3 administration in dyskinesia of rats with spinal cord injury. Yan-Wu G, Yi-Quan K, Ming L, Ying-Qian C, Xiao-Dan J, Shi-Zhong Z,
136. Differential activation of Toll-like receptor-mediated apoptosis induced by hypoxia. Mkaddem SB, Bens M, Vandewalle A, Oncotarget 2010 1 741 750 21321383
137. Toll-like receptor 4 ablation improves stem cell survival after hypoxic injury. Brewster BD, Rouch JD, Wang M, Meldrum DR, J Surg Res 2012 177 330 333 22703984
138. SDF-1alpha inhibits hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells through PI3K/Akt and ERK1/2 signaling pathways. Yin Q, Jin P, Liu X, Wei H, Lin X, Chi C, Liu Y, Sun C, Wei Y, Mol Biol Rep 2011 38 9 16 20383584
139. Overexpressing cellular repressor of E1A-stimulated genes protects mesenchymal stem cells against hypoxia- and serum deprivation-induced apoptosis by activation of PI3K/Akt. Deng J, Han Y, Yan C, Tian X, Tao J, Kang J, Li S, Apoptosis 2010 15 463 473 19997978
140. Carvedilol enhances mesenchymal stem cell therapy for myocardial infarction via inhibition of caspase-3 expression. Hassan F, Meduru S, Taguchi K, Kuppusamy ML, Mostafa M, Kuppusamy P, Khan M, J Pharmacol Exp Ther 2012 343 62 71 22739507
141. Inhibition of hypoxia and serum deprivation-induced apoptosis by salvianolic acid in rat mesenchymal stem cells. Cao W, Guo XW, Chen K, Xu RX, Zheng HZ, Wang J, J Tradit Chin Med 2012 32 222 228 22876447
142. Identification of microRNAs involved in hypoxia- and serum deprivation-induced apoptosis in mesenchymal stem cells. Nie Y, Han BM, Liu XB, Yang JJ, Wang F, Cong XF, Chen X, Int J Biol Sci 2011 7 762 768 21698002
143. Plasmid-based genetic modification of human bone marrow-derived stromal cells: analysis of cell survival and transgene expression after transplantation in rat spinal cord. Ronsyn MW, Daans J, Spaepen G, Chatterjee S, Vermeulen K, D'Haese P, Van Tendeloo VF, Van Marck E, Ysebaert D, Berneman ZN, Jorens PG, Ponsaerts P, BMC Biotechnol 2007 7 90 18078525