The secretome of apoptotic human peripheral blood mononuclear cells attenuates secondary damage following spinal cord injury in rats

Experimental Neurology

Volumn 267, Issue , 2015, Pages 230-242

  Haider, Thomas ^a   Höftberger, Romana ^b   Rüger, Beate ^a   Mildner, Michael ^c   Blumer, Roland ^a   Mitterbauer, Andreas ^a   Buchacher, Tanja ^a   Sherif, Camillo ^d   Altmann, Patrick ^a   Redl, Heinz ^e   Gabriel, Christian ^e,f   Gyöngyösi, Mariann ^a   Fischer, Michael B ^a,g   Lubec, Gert ^a   Ankersmit, Hendrik Jan ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

^c Universitatsklinik fur Dermatologie   (Austria)

^d KRANKENANSTALT RUDOLFSTIFTUNG   (Austria)

^e LUDWIG BOLTZMANN INSTITUTE FOR EXPERIMENTAL AND CLINICAL TRAUMATOLOGY   (Austria)

^f Red Cross Blood Transfusion Service of Upper Austria   (Austria)

^g DANUBE UNIVERSITY KREMS   (Austria)

Author keywords

Inflammation; MNC secretome; Oxidative stress; PBMCs; Secondary damage; Spinal cord injury; Traumatic spinal cord injury

Indexed keywords

BIOLOGICAL PRODUCT; CD68 ANTIGEN; CD68 ANTIGEN, HUMAN; CXCL1 CHEMOKINE; CYTOKINE; DIFFERENTIATION ANTIGEN; INDUCIBLE NITRIC OXIDE SYNTHASE; LEUKOCYTE ANTIGEN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; SECRETOME; UNCLASSIFIED DRUG; VASCULOTROPIN A;

ADULT; ANIMAL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AORTA; ARTICLE; AXONAL INJURY; BIOLOGICAL ACTIVITY; BIOLOGICAL THERAPY; BLOOD; CELL MIGRATION; CHEMISTRY; COMPLICATION; CONTROLLED STUDY; CONVALESCENCE; DISEASE MODEL; DRUG EFFECTS; ENZYME ACTIVATION; ETIOLOGY; GENE EXPRESSION REGULATION; HISTOPATHOLOGY; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IMMUNOLOGY; IN VIVO STUDY; INFLAMMATION; MALE; METABOLISM; MONONUCLEAR CELL; MOTOR ACTIVITY; MOTOR PERFORMANCE; NONHUMAN; OXIDATIVE STRESS; PATHOLOGY; PERIPHERAL BLOOD MONONUCLEAR CELL; PHYSIOLOGY; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; RAT; SECRETION (PROCESS); SPINAL CORD; SPINAL CORD INJURIES; SPINAL CORD INJURY; SPRAGUE DAWLEY RAT; THERAPY; TIME;

ANIMALS; ANTIGENS, CD; ANTIGENS, DIFFERENTIATION, MYELOMONOCYTIC; AORTA; BLOOD; CELL- AND TISSUE-BASED THERAPY; CHEMISTRY; CHEMOKINE CXCL1; COMPLICATIONS; CYTOKINES; DISEASE MODELS, ANIMAL; DRUG EFFECTS; ETIOLOGY; GENE EXPRESSION REGULATION; HUMANS; IMMUNOLOGY; INFLAMMATION; LEUKOCYTES, MONONUCLEAR; MALE; METABOLISM; MOTOR ACTIVITY; NITRIC OXIDE SYNTHASE TYPE II; OXIDATIVE STRESS; PATHOLOGY; PHYSIOLOGY; RATS; RATS, SPRAGUE-DAWLEY; RECOVERY OF FUNCTION; SECRETION; SPINAL CORD; SPINAL CORD INJURIES; THERAPY; TIME FACTORS; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84964224942     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2015.03.013     Document Type: Article

References (74)

1. Abrams M.B., Nilsson I., Lewandowski S.A., Kjell J., Codeluppi S., Olson L., Eriksson U. Imatinib enhances functional outcome after spinal cord injury. PLoS One 2012, 7:e38760.
2. Ackery A., Tator C., Krassioukov A. A global perspective on spinal cord injury epidemiology. J. Neurotrauma 2004, 21:1355-1370.
3. Altmann P., Mildner M., Haider T., Traxler D., Beer L., Ristl R., Golabi B., Gabriel C., Leutmezer F., Ankersmit H.J. Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats with focal ischemia 2014, F1000 Research.
4. Ankersmit H.J., Hoetzenecker K., Dietl W., Soleiman A., Horvat R., Wolfsberger M., Gerner C., Hacker S., Mildner M., Moser B., Lichtenauer M., Podesser B.K. Irradiated cultured apoptotic peripheral blood mononuclear cells regenerate infarcted myocardium. Eur. J. Clin. Invest. 2009, 39:445-456.
5. Aplin A.C., Fogel E., Zorzi P., Nicosia R.F. The aortic ring model of angiogenesis. Methods Enzymol. 2008, 443:119-136.
6. Bao F., Liu D. Peroxynitrite generated in the rat spinal cord induces neuron death and neurological deficits. Neuroscience 2002, 115:839-849.
7. Basso D.M., Beattie M.S., Bresnahan J.C. A sensitive and reliable locomotor rating scale for open field testing in rats. J. Neurotrauma 1995, 12:1-21.
8. Biswas S.K., Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 2010, 11:889-896.
9. Bowes A.L., Yip P. Modulating inflammatory cell responses to spinal cord injury: all in good time. J. Neurotrauma 2014, 31(21):1753-1766.
10. Boyd J.G., Gordon T. Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo. Exp. Neurol. 2003, 183:610-619.
11. Cadotte D.W., Fehlings M.G. Spinal cord injury: a systematic review of current treatment options. Clin. Orthop. Relat. Res. 2011, 469:732-741.
12. Cantinieaux D., Quertainmont R., Blacher S., Rossi L., Wanet T., Noel A., Brook G., Schoenen J., Franzen R. Conditioned medium from bone marrow-derived mesenchymal stem cells improves recovery after spinal cord injury in rats: an original strategy to avoid cell transplantation. PLoS One 2013, 8:e69515.
13. Carrion B., Janson I.A., Kong Y.P., Putnam A.J. A safe and efficient method to retrieve mesenchymal stem cells from three-dimensional fibrin gels. Tissue Eng. Part C Methods 2014, 20:252-263.
14. Chehrehasa F., Cobcroft M., Young Y.W., Mackay-Sim A., Goss B. An acute growth factor treatment that preserves function after spinal cord contusion injury. J. Neurotrauma 2014, 31(21):1807-1813.
15. Clark M.C., Baum L.G. T cells modulate glycans on CD43 and CD45 during development and activation, signal regulation, and survival. Ann. N. Y. Acad. Sci. 2012, 1253:58-67.
16. Filli L., Schwab M.E. The rocky road to translation in spinal cord repair. Ann. Neurol. 2012, 72:491-501.
17. Fleming J.C., Norenberg M.D., Ramsay D.A., Dekaban G.A., Marcillo A.E., Saenz A.D., Pasquale-Styles M., Dietrich W.D., Weaver L.C. The cellular inflammatory response in human spinal cords after injury. Brain 2006, 129:3249-3269.
18. Folkman J., Shing Y. Angiogenesis. J. Biol. Chem. 1992, 267:10931-10934.
19. Fu J., Fan H.B., Guo Z., Wang Z., Li X.D., Li J., Pei G.X. Salvianolic acid B attenuates spinal cord ischemia-reperfusion-induced neuronal injury and oxidative stress by activating the extracellular signal-regulated kinase pathway in rats. J. Surg. Res. 2014, 188:222-230.
20. Fuhler G.M., Knol G.J., Drayer A.L., Vellenga E. Impaired interleukin-8- and GROalpha-induced phosphorylation of extracellular signal-regulated kinase result in decreased migration of neutrophils from patients with myelodysplasia. J. Leukoc. Biol. 2005, 77:257-266.
21. Gehrmann J., Matsumoto Y., Kreutzberg G.W. Microglia: intrinsic immuneffector cell of the brain. Brain Res. Brain Res. Rev. 1995, 20:269-287.
22. Gnecchi M., He H., Liang O.D., Melo L.G., Morello F., Mu H., Noiseux N., Zhang L., Pratt R.E., Ingwall J.S., Dzau V.J. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat. Med. 2005, 11:367-368.
23. Gordon S., Taylor P.R. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 2005, 5:953-964.
24. Gschwandtner M., Zhong S., Tschachler A., Mlitz V., Karner S., Elbe-Burger A., Mildner M. Fetal human keratinocytes produce large amounts of antimicrobial peptides: involvement of histone-methylation processes. J. Invest. Dermatol. 2014, 134:2192-2201.
25. Hall E.D., Springer J.E. Neuroprotection and acute spinal cord injury: a reappraisal. NeuroRx 2004, 1:80-100.
26. Hall E.D., Vaishnav R.A., Mustafa A.G. Antioxidant therapies for traumatic brain injury. Neurotherapeutics 2010, 7:51-61.
27. Han H.E., Kim T.K., Son H.J., Park W.J., Han P.L. Activation of autophagy pathway suppresses the expression of iNOS, IL6 and cell death of LPS-stimulated microglia cells. Biomol. Ther. 2013, 21:21-28.
28. Hausmann O.N. Post-traumatic inflammation following spinal cord injury. Spinal Cord 2003, 41:369-378.
29. Hoetzenecker K., Assinger A., Lichtenauer M., Mildner M., Schweiger T., Starlinger P., Jakab A., Berenyi E., Pavo N., Zimmermann M., Gabriel C., Plass C., Gyongyosi M., Volf I., Ankersmit H.J. Secretome of apoptotic peripheral blood cells (APOSEC) attenuates microvascular obstruction in a porcine closed chest reperfused acute myocardial infarction model: role of platelet aggregation and vasodilation. Basic Res. Cardiol. 2012, 107:292.
30. Hoetzenecker K., Zimmermann M., Hoetzenecker W., Schweiger T., Kollmann D., Mildner M., Hegedus B., Mitterbauer A., Hacker S., Birner P., Gabriel C., Gyongyosi M., Blyszczuk P., Eriksson U., Ankersmit H.J. Mononuclear cell secretome protects from experimental autoimmune myocarditis. Eur. Heart J. 2015, 36(11):676-685.
31. Joseph R., Tsering C., Grunfeld S., Welch K.M. Platelet secretory products may contribute to neuronal injury. Stroke 1991, 22:1448-1451.
32. Joseph R., Saroff D.M., Delfs J.R. Platelet secretory products have a damaging effect on neurons. Neurosci. Lett. 1992, 135:153-158.
33. Kerlero de Rosbo N., Hoffman M., Mendel I., Yust I., Kaye J., Bakimer R., Flechter S., Abramsky O., Milo R., Karni A., Ben-Nun A. Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: reactivity to the extracellular domain of MOG is directed against three main regions. Eur. J. Immunol. 1997, 27:3059-3069.
34. Korf-Klingebiel M., Kempf T., Sauer T., Brinkmann E., Fischer P., Meyer G.P., Ganser A., Drexler H., Wollert K.C. Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction. Eur. Heart J. 2008, 29:2851-2858.
35. Kroner A., Greenhalgh A.D., Zarruk J.G., Passos Dos Santos R., Gaestel M., David S. TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. Neuron 2014, 83:1098-1116.
36. Kwon B.K., Tetzlaff W., Grauer J.N., Beiner J., Vaccaro A.R. Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J. 2004, 4:451-464.
37. Lee J.Y., Maeng S., Kang S.R., Choi H.Y., Oh T.H., Ju B.G., Yune T.Y. Valproic acid protects motor neuron death by inhibiting oxidative stress and endoplasmic reticulum stress-mediated cytochrome C release after spinal cord injury. J. Neurotrauma 2014, 31:582-594.
38. Lichtenauer M., Mildner M., Baumgartner A., Hasun M., Werba G., Beer L., Altmann P., Roth G., Gyongyosi M., Podesser B.K., Ankersmit H.J. Intravenous and intramyocardial injection of apoptotic white blood cell suspensions prevents ventricular remodelling by increasing elastin expression in cardiac scar tissue after myocardial infarction. Basic Res. Cardiol. 2011, 106:645-655.
39. Lichtenauer M., Mildner M., Hoetzenecker K., Zimmermann M., Podesser B.K., Sipos W., Berenyi E., Dworschak M., Tschachler E., Gyongyosi M., Ankersmit H.J. Secretome of apoptotic peripheral blood cells (APOSEC) confers cytoprotection to cardiomyocytes and inhibits tissue remodelling after acute myocardial infarction: a preclinical study. Basic Res. Cardiol. 2011, 106:1283-1297.
40. Lichtenauer M., Mildner M., Werba G., Beer L., Hoetzenecker K., Baumgartner A., Hasun M., Nickl S., Mitterbauer A., Zimmermann M., Gyongyosi M., Podesser B.K., Klepetko W., Ankersmit H.J. Anti-thymocyte globulin induces neoangiogenesis and preserves cardiac function after experimental myocardial infarction. PLoS One 2012, 7:e52101.
41. London A., Cohen M., Schwartz M. Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair. Front. Cell. Neurosci. 2013, 7:34.
42. Lutton C., Young Y.W., Williams R., Meedeniya A.C., Mackay-Sim A., Goss B. Combined VEGF and PDGF treatment reduces secondary degeneration after spinal cord injury. J. Neurotrauma 2012, 29:957-970.
43. Meeson A.P., Argilla M., Ko K., Witte L., Lang R.A. VEGF deprivation-induced apoptosis is a component of programmed capillary regression. Development 1999, 126:1407-1415.
44. Mildner M., Hacker S., Haider T., Gschwandtner M., Werba G., Barresi C., Zimmermann M., Golabi B., Tschachler E., Ankersmit H.J. Secretome of peripheral blood mononuclear cells enhances wound healing. PLoS One 2013, 8:e60103.
45. Mirotsou M., Jayawardena T.M., Schmeckpeper J., Gnecchi M., Dzau V.J. Paracrine mechanisms of stem cell reparative and regenerative actions in the heart. J. Mol. Cell. Cardiol. 2011, 50:280-289.
46. Miyake M., Goodison S., Urquidi V., Gomes Giacoia E., Rosser C.J. Expression of CXCL1 in human endothelial cells induces angiogenesis through the CXCR2 receptor and the ERK1/2 and EGF pathways. Lab. Invest. 2013, 93:768-778.
47. Murray P.J., Wynn T.A. Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 2011, 11:723-737.
48. Nicosia R.F., Ottinetti A. Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro. Lab. Invest. 1990, 63:115-122.
49. Omari K.M., Lutz S.E., Santambrogio L., Lira S.A., Raine C.S. Neuroprotection and remyelination after autoimmune demyelination in mice that inducibly overexpress CXCL1. Am. J. Pathol. 2009, 174:164-176.
50. Oyinbo C.A. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol. Exp. 2011, 71:281-299.
51. Pavo N., Zimmermann M., Pils D., Mildner M., Petrasi Z., Petnehazy O., Fuzik J., Jakab A., Gabriel C., Sipos W., Maurer G., Gyongyosi M., Ankersmit H.J. Long-acting beneficial effect of percutaneously intramyocardially delivered secretome of apoptotic peripheral blood cells on porcine chronic ischemic left ventricular dysfunction. Biomaterials 2014, 35:3541-3550.
52. Perotti C., Arici V., Cervio M., Del Fante C., Calliada F., Gnecchi M., Ciuffreda M.C., Scudeller L., Bozzani A., Ragni F., Viarengo G., Cervio E., Odero A., Redi C.A. Allogeneic lethally irradiated cord blood mononuclear cells in no-option critical limb ischemia: a "box of rain". Stem Cells Dev. 2013, 22:2806-2812.
53. Popovich P.G., Hickey W.F. Bone marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord. J. Neuropathol. Exp. Neurol. 2001, 60:676-685.
54. Popovich P.G., Wei P., Stokes B.T. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J. Comp. Neurol. 1997, 377:443-464.
55. Quertainmont R., Cantinieaux D., Botman O., Sid S., Schoenen J., Franzen R. Mesenchymal stem cell graft improves recovery after spinal cord injury in adult rats through neurotrophic and pro-angiogenic actions. PLoS One 2012, 7:e39500.
56. Rapalino O., Lazarov-Spiegler O., Agranov E., Velan G.J., Yoles E., Fraidakis M., Solomon A., Gepstein R., Katz A., Belkin M., Hadani M., Schwartz M. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat. Med. 1998, 4:814-821.
57. Ravikumar R., McEwen M.L., Springer J.E. Post-treatment with the cyclosporin derivative, NIM811, reduced indices of cell death and increased the volume of spared tissue in the acute period following spinal cord contusion. J. Neurotrauma 2007, 24:1618-1630.
58. Rowland J.W., Hawryluk G.W., Kwon B., Fehlings M.G. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg. Focus 2008, 25:E2.
59. Ruger B.M., Breuss J., Hollemann D., Yanagida G., Fischer M.B., Mosberger I., Chott A., Lang I., Davis P.F., Hocker P., Dettke M. Vascular morphogenesis by adult bone marrow progenitor cells in three-dimensional fibrin matrices. Differentiation 2008, 76:772-783.
60. Scheff S.W., Rabchevsky A.G., Fugaccia I., Main J.A., Lumpp J.E. Experimental modeling of spinal cord injury: characterization of a force-defined injury device. J. Neurotrauma 2003, 20:179-193.
61. Seghatchian J., Struff W.G., Reichenberg S. Main properties of the THERAFLEX MB-plasma system for pathogen reduction. Transfus. Med. Hemother. 2011, 38:55-64.
62. Shechter R., London A., Varol C., Raposo C., Cusimano M., Yovel G., Rolls A., Mack M., Pluchino S., Martino G., Jung S., Schwartz M. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med. 2009, 6:e1000113.
63. Song X.Y., Li F., Zhang F.H., Zhong J.H., Zhou X.F. Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury. PLoS One 2008, 3:e1707.
64. Sotnikov I., Veremeyko T., Starossom S.C., Barteneva N., Weiner H.L., Ponomarev E.D. Platelets recognize brain-specific glycolipid structures, respond to neurovascular damage and promote neuroinflammation. PLoS One 2013, 8:e58979.
65. Teixeira F.G., Carvalho M.M., Sousa N., Salgado A.J. Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration?. Cell. Mol. Life Sci. 2013, 70:3871-3882.
66. Thornton P., McColl B.W., Greenhalgh A., Denes A., Allan S.M., Rothwell N.J. Platelet interleukin-1alpha drives cerebrovascular inflammation. Blood 2010, 115:3632-3639.
67. Thurston G., Gale N.W. Vascular endothelial growth factor and other signaling pathways in developmental and pathologic angiogenesis. Int. J. Hematol. 2004, 80:7-20.
68. Toborek M., Son K.W., Pudelko A., King-Pospisil K., Wylegala E., Malecki A. ERK 1/2 signaling pathway is involved in nicotine-mediated neuroprotection in spinal cord neurons. J. Cell. Biochem. 2007, 100:279-292.
69. Tseliou E., de Couto G., Terrovitis J., Sun B., Weixin L., Marban L., Marban E. Angiogenesis, cardiomyocyte proliferation and anti-fibrotic effects underlie structural preservation post-infarction by intramyocardially-injected cardiospheres. PLoS One 2014, 9:e88590.
70. Tuszynski M.H., Steward O. Concepts and methods for the study of axonal regeneration in the CNS. Neuron 2012, 74:777-791.
71. Wei L., Zhang J., Xiao X.B., Mai H.X., Zheng K., Sun W.L., Wang L., Liang F., Yang Z.L., Liu Y., Wang Y.Q., Li Z.F., Wang J.N., Zhang W.J., You H. Multiple injections of human umbilical cord-derived mesenchymal stromal cells through the tail vein improve microcirculation and the microenvironment in a rat model of radiation myelopathy. J. Transl. Med. 2014, 12:246.
72. Wenjin W., Wenchao L., Hao Z., Feng L., Yan W., Wodong S., Xianqun F., Wenlong D. Electrical stimulation promotes BDNF expression in spinal cord neurons through Ca(2+)- and Erk-dependent signaling pathways. Cell. Mol. Neurobiol. 2011, 31:459-467.
73. Wright K.T., El Masri W., Osman A., Chowdhury J., Johnson W.E. Concise review: bone marrow for the treatment of spinal cord injury: mechanisms and clinical applications. Stem Cells 2011, 29:169-178.
74. Yune T.Y., Chang M.J., Kim S.J., Lee Y.B., Shin S.W., Rhim H., Kim Y.C., Shin M.L., Oh Y.J., Han C.T., Markelonis G.J., Oh T.H. Increased production of tumor necrosis factor-alpha induces apoptosis after traumatic spinal cord injury in rats. J. Neurotrauma 2003, 20:207-219.