nach oben

Erschienen in:

25.05.2017 | Original Article

Stroke Induces Mesenchymal Stem Cell Migration to Infarcted Brain Areas Via CXCR4 and C-Met Signaling

verfasst von: Oh Young Bang, Gyeong Joon Moon, Dong Hee Kim, Ji Hyun Lee, Sooyoon Kim, Jeong Pyo Son, Yeon Hee Cho, Won Hyuk Chang, Yun-Hee Kim, the STARTING-2 trial investigators

Erschienen in: Translational Stroke Research | Ausgabe 5/2017

Einloggen, um Zugang zu erhalten

Abstract

Mesenchymal stem cells circulate between organs to repair and maintain tissues. Mesenchymal stem cells cultured with fetal bovine serum have therapeutic effects when intravenously administered after stroke. However, only a small number of mesenchymal stem cells reach the brain. We hypothesized that the serum from stroke patients increases mesenchymal stem cells trophism toward the infarcted brain area. Mesenchymal stem cells were grown in fetal bovine serum, normal serum from normal rats, or stroke serum from ischemic stroke rats. Compared to the fetal bovine serum group, the stroke serum group but not the normal serum group showed significantly greater migration toward the infarcted brain area in the in vitro and in vivo models (p < 0.05). Both C-X-C chemokine receptor type 4 and c-Met expression levels significantly increased in the stroke serum group than the others. The enhanced mesenchymal stem cells migration of the stroke serum group was abolished by inhibition of signaling. Serum levels of chemokines, cytokines, matrix metalloproteinase, and growth factors were higher in stroke serum than in normal serum. Behavioral tests showed a significant improvement in the recovery after stroke in the stroke serum group than the others. Stroke induces mesenchymal stem cells migration to the infarcted brain area via C-X-C chemokine receptor type 4 and c-Met signaling. Culture expansion using the serum from stroke patients could constitute a novel preconditioning method to enhance the therapeutic efficiency of mesenchymal stem cells.

Nur mit Berechtigung zugänglich

Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol. 2005;57(6):874–82. doi:10.1002/ana.20501.CrossRefPubMed

Honmou O, Houkin K, Matsunaga T, Niitsu Y, Ishiai S, Onodera R, et al. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain. 2011;134(Pt 6):1790–807. doi:10.1093/brain/awr063.CrossRefPubMedPubMedCentral

Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells. 2010;28(6):1099–106. doi:10.1002/stem.430.CrossRefPubMed

Savitz SI, Dinsmore J, Wu J, Henderson GV, Stieg P, Caplan LR. Neurotransplantation of fetal porcine cells in patients with basal ganglia infarcts: a preliminary safety and feasibility study. Cerebrovasc Dis. 2005;20(2):101–7. doi:10.1159/000086518.CrossRefPubMed

Savitz SI, Misra V, Kasam M, Juneja H, Cox CS Jr, Alderman S, et al. Intravenous autologous bone marrow mononuclear cells for ischemic stroke. Ann Neurol. 2011;70(1):59–69. doi:10.1002/ana.22458.CrossRefPubMed

Sprigg N, Bath PM, Zhao L, Willmot MR, Gray LJ, Walker MF, et al. Granulocyte-colony-stimulating factor mobilizes bone marrow stem cells in patients with subacute ischemic stroke: the Stem cell Trial of recovery EnhanceMent after Stroke (STEMS) pilot randomized, controlled trial (ISRCTN 16784092). Stroke. 2006;37(12):2979–83. doi:10.1161/01.STR.0000248763.49831.c3.CrossRefPubMed

Bang OY. Clinical trials of adult stem cell therapy in patients with ischemic stroke. J Clin Neurol. 2016;12(1):14–20. doi:10.3988/jcn.2016.12.1.14.CrossRefPubMed

Lindvall O, Kokaia Z. Recovery and rehabilitation in stroke: stem cells. Stroke. 2004;35(11 Suppl 1):2691–4. doi:10.1161/01.STR.0000143323.84008.f4.CrossRefPubMed

Pendharkar AV, Chua JY, Andres RH, Wang N, Gaeta X, Wang H, et al. Biodistribution of neural stem cells after intravascular therapy for hypoxic-ischemia. Stroke. 2010;41(9):2064–70. doi:10.1161/STROKEAHA.109.575993.CrossRefPubMedPubMedCentral

10.

Kang WJ, Kang HJ, Kim HS, Chung JK, Lee MC, Lee DS. Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. J Nucl Med. 2006;47(8):1295–301.PubMed

11.

Li WY, Choi YJ, Lee PH, Huh K, Kang YM, Kim HS, et al. Mesenchymal stem cells for ischemic stroke: changes in effects after ex vivo culturing. Cell Transplant. 2008;17(9):1045–59.CrossRefPubMed

12.

Kim SJ, Moon GJ, Chang WH, Kim YH, Bang OY. Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial. Trials. 2013;14(1):317. doi:10.1186/1745-6215-14-317.CrossRefPubMedPubMedCentral

13.

Shin JH, Park YM, Kim DH, Moon GJ, Bang OY, Ohn T, et al. Ischemic brain extract increases SDF-1 expression in astrocytes through the CXCR2/miR-223/miR-27b pathway. Biochim Biophys Acta. 2014;1839(9):826–36. doi:10.1016/j.bbagrm.2014.06.019.CrossRefPubMed

14.

Kim DH, Seo YK, Thambi T, Moon GJ, Son JP, Li G, et al. Enhancing neurogenesis and angiogenesis with target delivery of stromal cell derived factor-1alpha using a dual ionic pH-sensitive copolymer. Biomaterials. 2015;61:115–25. doi:10.1016/j.biomaterials.2015.05.025.CrossRefPubMed

15.

Moon GJ, Shin DH, Im DS, Bang OY, Nam HS, Lee JH, et al. Identification of oxidized serum albumin in the cerebrospinal fluid of ischaemic stroke patients. Eur J Neurol. 2011;18(9):1151–8. doi:10.1111/j.1468-1331.2011.03357.x.CrossRefPubMed

16.

Zacharek A, Shehadah A, Chen J, Cui X, Roberts C, Lu M, et al. Comparison of bone marrow stromal cells derived from stroke and normal rats for stroke treatment. Stroke. 2010;41(3):524–30. doi:10.1161/STROKEAHA.109.568881.CrossRefPubMedPubMedCentral

17.

Rosado-de-Castro PH, Schmidt Fda R, Battistella V, Lopes de Souza SA, Gutfilen B, Goldenberg RC et al. Biodistribution of bone marrow mononuclear cells after intra-arterial or intravenous transplantation in subacute stroke patients. Regen Med 2013;8(2):145–155. doi:10.2217/rme.13.2.

18.

Rosenblum S, Wang N, Smith TN, Pendharkar AV, Chua JY, Birk H, et al. Timing of intra-arterial neural stem cell transplantation after hypoxia-ischemia influences cell engraftment, survival, and differentiation. Stroke. 2012;43(6):1624–31. doi:10.1161/STROKEAHA.111.637884.CrossRefPubMed

19.

Dimmeler S, Ding S, Rando TA, Trounson A. Translational strategies and challenges in regenerative medicine. Nat Med. 2014;20(8):814–21. doi:10.1038/nm.3627.CrossRefPubMed

20.

Yang B, Migliati E, Parsha K, Schaar K, Xi X, Aronowski J, et al. Intra-arterial delivery is not superior to intravenous delivery of autologous bone marrow mononuclear cells in acute ischemic stroke. Stroke. 2013;44(12):3463–72. doi:10.1161/STROKEAHA.111.000821.CrossRefPubMedPubMedCentral

21.

Bang OY, Jin KS, Hwang MN, Kang HY, Kim BJ, Lee SJ, et al. The effect of CXCR4 overexpression on mesenchymal stem cell transplantation in ischemic stroke. Cell Med. 2012;4:65–76.CrossRefPubMedPubMedCentral

22.

Cutler C, Multani P, Robbins D, Kim HT, Le T, Hoggatt J, et al. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood. 2013;122(17):3074–81. doi:10.1182/blood-2013-05-503177.CrossRefPubMedPubMedCentral

23.

Zaruba MM, Theiss HD, Vallaster M, Mehl U, Brunner S, David R, et al. Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction. Cell Stem Cell. 2009;4(4):313–23. doi:10.1016/j.stem.2009.02.013.CrossRefPubMed

24.

Cui X, Chen J, Zacharek A, Li Y, Roberts C, Kapke A, et al. Nitric oxide donor upregulation of stromal cell-derived factor-1/chemokine (CXC motif) receptor 4 enhances bone marrow stromal cell migration into ischemic brain after stroke. Stem Cells. 2007;25(11):2777–85. doi:10.1634/stemcells.2007-0169.CrossRefPubMedPubMedCentral

25.

Pons J, Huang Y, Arakawa-Hoyt J, Washko D, Takagawa J, Ye J, et al. VEGF improves survival of mesenchymal stem cells in infarcted hearts. Biochem Biophys Res Commun. 2008;376(2):419–22. doi:10.1016/j.bbrc.2008.09.003.CrossRefPubMed

26.

Liu H, Xue W, Ge G, Luo X, Li Y, Xiang H, et al. Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1alpha in MSCs. Biochem Biophys Res Commun. 2010;401(4):509–15. doi:10.1016/j.bbrc.2010.09.076.CrossRefPubMed

27.

Francis KR, Wei L. Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning. Cell Death Dis. 2010;1:e22. doi:10.1038/cddis.2009.22.CrossRefPubMedPubMedCentral

28.

Hu X, Yu SP, Fraser JL, Lu Z, Ogle ME, Wang JA, et al. Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. J Thorac Cardiovasc Surg. 2008;135(4):799–808. doi:10.1016/j.jtcvs.2007.07.071.CrossRefPubMed

29.

Theus MH, Wei L, Cui L, Francis K, Hu X, Keogh C, et al. 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. Exp Neurol. 2008;210(2):656–70. doi:10.1016/j.expneurol.2007.12.020.CrossRefPubMed

30.

Pasha Z, Wang Y, Sheikh R, Zhang D, Zhao T, Ashraf M. Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. Cardiovasc Res. 2008;77(1):134–42. doi:10.1093/cvr/cvm025.CrossRefPubMed

31.

Ancelin M, Chollet-Martin S, Herve MA, Legrand C, El Benna J, Perrot-Applanat M. Vascular endothelial growth factor VEGF189 induces human neutrophil chemotaxis in extravascular tissue via an autocrine amplification mechanism. Lab Investig. 2004;84(4):502–12. doi:10.1038/labinvest.3700053.CrossRefPubMed

32.

Zigmond SH, Hirsch JG. Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor. J Exp Med. 1973;137(2):387–410.CrossRefPubMedPubMedCentral

33.

Ehrenfeld P, Millan C, Matus CE, Figueroa JE, Burgos RA, Nualart F, et al. Activation of kinin B1 receptors induces chemotaxis of human neutrophils. J Leukoc Biol. 2006;80(1):117–24. doi:10.1189/jlb.1205744.CrossRefPubMed

34.

Deng C, Qin A, Zhao W, Feng T, Shi C, Liu T. Up-regulation of CXCR4 in rat umbilical mesenchymal stem cells induced by serum from rat with acute liver failure promotes stem cells migration to injured liver tissue. Mol Cell Biochem. 2014; doi:10.1007/s11010-014-2147-7.

35.

Son BR, Marquez-Curtis LA, Kucia M, Wysoczynski M, Turner AR, Ratajczak J, et al. Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells. 2006;24(5):1254–64. doi:10.1634/stemcells.2005-0271.CrossRefPubMed

36.

Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells. 2006;24(4):1030–41. doi:10.1634/stemcells.2005-0319.CrossRefPubMed

37.

Li Y, Yu X, Lin S, Li X, Zhang S, Song YH. Insulin-like growth factor 1 enhances the migratory capacity of mesenchymal stem cells. Biochem Biophys Res Commun. 2007;356(3):780–4. doi:10.1016/j.bbrc.2007.03.049.CrossRefPubMed

38.

Bhakta S, Hong P, Koc O. The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovas Revasc Med. 2006;7(1):19–24. doi:10.1016/j.carrev.2005.10.008.CrossRef

39.

Ono K, Matsumori A, Shioi T, Furukawa Y, Sasayama S. Enhanced expression of hepatocyte growth factor/c-Met by myocardial ischemia and reperfusion in a rat model. Circulation. 1997;95(11):2552–8.CrossRefPubMed

40.

Chen X, Li Y, Wang L, Katakowski M, Zhang L, Chen J, et al. Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology. 2002;22(4):275–9.CrossRefPubMed

41.

Tacchini L, De Ponti C, Matteucci E, Follis R, Desiderio MA. Hepatocyte growth factor-activated NF-kappaB regulates HIF-1 activity and ODC expression, implicated in survival, differently in different carcinoma cell lines. Carcinogenesis. 2004;25(11):2089–100. doi:10.1093/carcin/bgh227.CrossRefPubMed

42.

Tacchini L, Dansi P, Matteucci E, Desiderio MA. Hepatocyte growth factor signalling stimulates hypoxia inducible factor-1 (HIF-1) activity in HepG2 hepatoma cells. Carcinogenesis. 2001;22(9):1363–71.CrossRefPubMed

43.

Kohler T, Reizis B, Johnson RS, Weighardt H, Forster I. Influence of hypoxia-inducible factor 1alpha on dendritic cell differentiation and migration. Eur J Immunol. 2012;42(5):1226–36. doi:10.1002/eji.201142053.CrossRefPubMed

44.

Choi JH, Lee YB, Jung J, Hwang SG, Oh IH, Kim GJ. Hypoxia inducible factor-1alpha regulates the migration of bone marrow mesenchymal stem cells via integrin alpha 4. Stem Cells Int. 2016;2016:7932185. doi:10.1155/2016/7932185.CrossRefPubMedPubMedCentral

45.

Hot A, Zrioual S, Lenief V, Miossec P. IL-17 and tumour necrosis factor alpha combination induces a HIF-1alpha-dependent invasive phenotype in synoviocytes. Ann Rheum Dis. 2012;71(8):1393–401. doi:10.1136/annrheumdis-2011-200867.CrossRefPubMed

46.

Scharte M, Han X, Bertges DJ, Fink MP, Delude RL. Cytokines induce HIF-1 DNA binding and the expression of HIF-1-dependent genes in cultured rat enterocytes. Am J Physiol Gastrointest Liver Physiol. 2003;284(3):G373–84. doi:10.1152/ajpgi.00076.2002.CrossRefPubMed

47.

Nakamura K, Martin KC, Jackson JK, Beppu K, Woo CW, Thiele CJ. Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial growth factor expression via hypoxia-inducible factor-1alpha in neuroblastoma cells. Cancer Res. 2006;66(8):4249–55. doi:10.1158/0008-5472.CAN-05-2789.CrossRefPubMed

48.

Shi YH, Wang YX, Bingle L, Gong LH, Heng WJ, Li Y, et al. In vitro study of HIF-1 activation and VEGF release by bFGF in the T47D breast cancer cell line under normoxic conditions: involvement of PI-3K/Akt and MEK1/ERK pathways. J Pathol. 2005;205(4):530–6. doi:10.1002/path.1734.CrossRefPubMed

49.

Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu MM, et al. Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res. 2000;60(6):1541–5.PubMed

50.

Slomiany MG, Rosenzweig SA. IGF-1-induced VEGF and IGFBP-3 secretion correlates with increased HIF-1 alpha expression and activity in retinal pigment epithelial cell line D407. Invest Ophthalmol Vis Sci. 2004;45(8):2838–47. doi:10.1167/iovs.03-0565.CrossRefPubMed

51.

McMahon S, Charbonneau M, Grandmont S, Richard DE, Dubois CM. Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression. J Biol Chem. 2006;281(34):24171–81. doi:10.1074/jbc.M604507200.CrossRefPubMed

52.

Chu SH, Ma YB, Zhang H, Feng DF, Zhu ZA, Li ZQ, et al. Hepatocyte growth factor production is stimulated by gangliosides and TGF-beta isoforms in human glioma cells. J Neuro-Oncol. 2007;85(1):33–8. doi:10.1007/s11060-007-9387-2.CrossRef

53.

Lewis MP, Lygoe KA, Nystrom ML, Anderson WP, Speight PM, Marshall JF, et al. Tumour-derived TGF-beta1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells. Br J Cancer. 2004;90(4):822–32. doi:10.1038/sj.bjc.6601611.CrossRefPubMedPubMedCentral

54.

Takami Y, Motoki T, Yamamoto I, Gohda E. Synergistic induction of hepatocyte growth factor in human skin fibroblasts by the inflammatory cytokines interleukin-1 and interferon-gamma. Biochem Biophys Res Commun. 2005;327(1):212–7. doi:10.1016/j.bbrc.2004.11.144.CrossRefPubMed

55.

Zagzag D, Lukyanov Y, Lan L, Ali MA, Esencay M, Mendez O, et al. Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion. Lab Investig. 2006;86(12):1221–32. doi:10.1038/labinvest.3700482.CrossRefPubMed

56.

Zhao Y, Matsuo-Takasaki M, Tsuboi I, Kimura K, Salazar GT, Yamashita T, et al. Dual functions of hypoxia-inducible factor 1 alpha for the commitment of mouse embryonic stem cells toward a neural lineage. Stem Cells Dev. 2014;23(18):2143–55. doi:10.1089/scd.2013.0278.CrossRefPubMed

57.

Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995;92(12):5510–4.CrossRefPubMedPubMedCentral

Titel: Stroke Induces Mesenchymal Stem Cell Migration to Infarcted Brain Areas Via CXCR4 and C-Met Signaling
verfasst von: Oh Young Bang
Gyeong Joon Moon
Dong Hee Kim
Ji Hyun Lee
Sooyoon Kim
Jeong Pyo Son
Yeon Hee Cho
Won Hyuk Chang
Yun-Hee Kim
the STARTING-2 trial investigators
Publikationsdatum: 25.05.2017
Verlag: Springer US
Erschienen in: Translational Stroke Research / Ausgabe 5/2017
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-017-0538-2

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

25.04.2024 | Hypotonie | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Stroke Induces Mesenchymal Stem Cell Migration to Infarcted Brain Areas Via CXCR4 and C-Met Signaling

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Neurologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2017

Biomarkers of Acute Stroke Etiology (BASE) Study Methodology

Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the Subventricular Zone

Precision Stroke Animal Models: the Permanent MCAO Model Should Be the Primary Model, Not Transient MCAO

Diabetes Worsens Functional Outcomes in Young Female Rats: Comparison of Stroke Models, Tissue Plasminogen Activator Effects, and Sexes

Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage: Causal in Cerebellar Damage?

Emerging Roles of Sirtuins in Ischemic Stroke

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Neurologie