Skip to main content
SpringerLink
Log in

TNF-α modulates the migratory response of mesenchymal stem cells to TRAIL

  • Research Article
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

The number of circulating mesenchymal stem cells (MSC), analyzed after acute myocardial infarction (AMI), was lower in AMI patients who developed heart failure (HF) in the follow-up. Conversely, the circulating levels of tumor necrosis factor (TNF)-α, and osteoprotegerin (OPG) were higher in AMI patients who developed HF with respect to the patients who did not develop HF. In vitro exposure to TNF-α enhanced the migration of MSC in response to TNF-related apoptosis-inducing ligand (TRAIL) and significantly increased the release of OPG by endothelial cells. On the contrary, OPG dose-dependently neutralized the in vitro pro-migratory activity of TRAIL. Thus, TNF-α exhibits opposite effects on MSC migration driven by TRAIL: it is capable of potentiating MSC migration as well as of inhibiting MSC migration as an indirect consequence of OPG induction, which might result in a suboptimal recruitment of circulating MSC after AMI in those patients who develop HF in the follow-up.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Torre-Amione G, Kapadia S, Lee J, Durand JB, Bies RD, Young JB, Mann DL (1996) Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart. Circulation 93:704–711

    CAS  PubMed  Google Scholar 

  2. Feldman AM, Combes A, Wagner D, Kadokami T, Kubota T, Li YY, McTiernan C (2000) The role of tumor necrosis factor in the pathophysiology of heart failure. J Am Coll Cardiol 35:537–544

    Article  CAS  PubMed  Google Scholar 

  3. Sun M, Dawood F, Wen WH, Chen M, Dixon I, Kirshenbaum LA, Liu PP (2004) Excessive tumor necrosis factor activation after infarction contributes to susceptibility of myocardial rupture and left ventricular dysfunction. Circulation 110:3221–3228

    Article  CAS  PubMed  Google Scholar 

  4. Akasaka Y, Morimoto N, Ishikawa Y, Fujita K, Ito K, Kimura-Matsumoto M, Ishiguro S, Morita H, Kobayashi Y, Ishii T (2006) Myocardial apoptosis associated with the expression of proinflammatory cytokines during the course of myocardial infarction. Mod Pathol 19:588–598

    Article  CAS  PubMed  Google Scholar 

  5. Kim YS, Park HJ, Hong MH, Kang PM, Morgan JP, Jeong MH, Cho JG, Park JC, Ahn Y (2009) TNF-alpha enhances engraftment of mesenchymal stem cells into infarcted myocardium. Front Biosci 14:2845–2856

    Article  CAS  PubMed  Google Scholar 

  6. Sun J, Li SH, Liu SM, Wu J, Weisel RD, Zhuo YF, Yau TM, Li RK, Fazel SS (2009) Improvement in cardiac function after bone marrow cell therapy is associated with an increase in myocardial inflammation. Am J Physiol Heart Circ Physiol 296:H43–H50

    Article  CAS  PubMed  Google Scholar 

  7. Simonet WS, Lacey DL, Dunstan C, Kelly M, Chang MS, Luthy R, Nhuyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliot R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319

    Article  CAS  PubMed  Google Scholar 

  8. Zauli G, Secchiero P (2006) The role of the TRAIL/TRAIL receptors system in hematopoiesis and endothelial cell biology. Cytokine Growth Fact Rev 17:245–257

    Article  CAS  Google Scholar 

  9. Jono S, Ikari Y, Shioi A, Mori K, Miki T, Hara K, Nishizawa Y (2002) Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 106:1192–1194

    Article  CAS  PubMed  Google Scholar 

  10. Schoppet M, Sattler AM, Schaefer JR, Herzum M, Maisch B, Hofbauer LC (2003) Increased osteoprotegerin serum levels in men with coronary artery disease. J Clin Endocrinol Metab 88:1024–1028

    Article  CAS  PubMed  Google Scholar 

  11. Ueland T, Jemtland R, Godang K, Kjekshus J, Hognestad A, Omland T, Squire IB, Gullestad L, Bollerslev J, Dickstein K, Aukrust P (2004) Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction. J Am Coll Cardiol 44:1970–1976

    Article  CAS  PubMed  Google Scholar 

  12. Kiechl S, Schett G, Wenning G, Redlich K, Oberhollenzer M, Mayr A, Santer P, Smolen J, Poewe W, Willeit J (2004) Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 109:2175–2180

    Article  CAS  PubMed  Google Scholar 

  13. Ueland T, Yndestad A, Øie E, Florholmen G, Halvorsen B, Frøland SS, Simonsen S, Christensen G, Gullestad L, Aukrust P (2005) Dysregulated osteoprotegerin/RANK ligand/RANK axis in clinical and experimental heart failure. Circulation 111:2461–2468

    Article  CAS  PubMed  Google Scholar 

  14. Avignon A, Sultan A, Piot C, Elaerts S, Cristol JP, Dupuy AM (2005) Osteoprotegerin is associated with silent coronary artery disease in high-risk but asymptomatic type 2 diabetic patients. Diabetes Care 28:2176–2180

    Article  CAS  PubMed  Google Scholar 

  15. Shin JY, Shin YG, Chun CH (2006) Elevated serum osteoprotegerin levels are associated with vascular endothelial dysfunction in type 2 diabetes. Diabetes Care 29:1664–1666

    Article  CAS  PubMed  Google Scholar 

  16. Secchiero P, Corallini F, Pandolfi A, Consoli A, Candido R, Fabris B, Celeghini C, Capitani S, Zauli G (2006) An increased osteoprotegerin (OPG) serum release characterizes the early onset of diabetes mellitus and may contribute to endothelial cell dysfunction. Am J Pathol 169:2236–2244

    Article  CAS  PubMed  Google Scholar 

  17. Abedin M, Omland T, Ueland T, Khera A, Aukrust P, Murphy SA, Jain T, Gruntmanis U, McGuire DK, de Lemos JA (2007) Relation of osteoprotegerin to coronary calcium and aortic plaque. Am J Cardiol 99:513–518

    Article  CAS  PubMed  Google Scholar 

  18. Helske S, Kovanen PT, Lindstedt KA, Salmela K, Lommi J, Turto H, Werkkala K, Kupari M (2007) Increased circulating concentrations and augmented myocardial extraction of osteoprotegerin in heart failure due to left ventricular pressure overload. Eur J Heart Fail 28:1894–1903

    CAS  Google Scholar 

  19. Omland T, Ueland T, Jansson AM, Persson A, Karlsson T, Smith C, Herlitz J, Aukrust P, Hartford M, Caidahl K (2008) Circulating osteoprotegerin levels and long-term prognosis in patients with acute coronary syndromes. J Am Coll Cardiol 51:627–633

    Article  CAS  PubMed  Google Scholar 

  20. Nybo M, Rasmussen L (2008) The capability of plasma osteoprotegerin as a predictor of cardiovascular disease. A systematic literature review. Eur J Endocrinol 159:603–608

    Article  CAS  PubMed  Google Scholar 

  21. Secchiero P, Corallini F, Ceconi C, Parrinello G, Volpato S, Ferrari R, Zauli G (2009) Potential prognostic significance of decreased serum levels of TRAIL after acute myocardial infarction. PLoS One 4:e4442

    Article  PubMed  Google Scholar 

  22. Niessner A, Hohensinner PJ, Rychli K, Neuhold S, Zorn G, Richter B, Hülsmann M, Berger R, Mörtl D, Huber K, Wojta J, Pacher R (2009) Prognostic value of apoptosis markers in advanced heart failure patients. Eur Heart J 30:789–796

    Article  CAS  PubMed  Google Scholar 

  23. Satoh D, Inami N, Shimazu T, Kajiura T, Yamada K, Iwasaka T, Nomura S (2009) Soluble TRAIL prevents RANTES-dependent restenosis after percutaneous coronary intervention in patients with coronary artery disease. J Thromb Thrombolysis doi:10.1007/s11239-009-0364-9

  24. Li SC, Wang L, Jiang H, Acevedo J, Chang AC, Loudon WG (2009) Stem cell engineering for treatment of heart diseases: potentials and challenges. Cell Biol Int 33:255–267

    Article  CAS  PubMed  Google Scholar 

  25. Secchiero P, Melloni E, Corallini F, Beltrami AP, Alviano F, Milani D, D’Aurizio F, di Iasio MG, Cesselli D, Bagnara GP, Zauli G (2008) Tumor necrosis factor-related apoptosis-inducing ligand promotes migration of human bone marrow multipotent stroma cells. Stem Cells 26:2955–2963

    Article  CAS  PubMed  Google Scholar 

  26. The Joint European Society of Cardiology/American College of Cardiology Committee (2000) Myocardial infarction redefined—a consensus document for the redefinition of myocardial infarction. Eur Heart J 21:1502–1513

    Google Scholar 

  27. The Task Force on Heart Failure of the European Society of Cardiology (1995) Guidelines for the diagnosis of heart failure. Eur Heart J 16:741–751

    Google Scholar 

  28. Secchiero P, Zerbinati C, Rimondi E, Corallini F, Milani D, Grill V, Forti G, Capitani S, Zauli G (2004) TRAIL promotes the survival, migration and proliferation of vascular smooth muscle cells. Cell Mol Life Sci 61:1965–1974

    Article  CAS  PubMed  Google Scholar 

  29. Milani D, Zauli G, Rimondi E, Celeghini C, Marmiroli S, Narducci P, Capitani S, Secchiero P (2003) Tumour necrosis factor-related apoptosis-inducing ligand sequentially activates pro-survival and pro-apoptotic pathways in SK-N-MC neuronal cells. J Neurochem 86:126–135

    Article  CAS  PubMed  Google Scholar 

  30. Ponte AL, Marais E, Gallay N, Langonné A, Delorme B, Hérault O, Charbord P, Domenech J (2007) The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 25:1737–1745

    Article  CAS  PubMed  Google Scholar 

  31. Zauli G, Melloni E, Capitani S, Secchiero P (2009) Role of full-length osteoprotegerin in tumor cell biology. Cell Mol Life Sci 66:841–851

    Article  CAS  PubMed  Google Scholar 

  32. Massa M, Rosti V, Ferrario M, Campanelli R, Ramajoli I, Rosso R, De Ferrari GM, Ferlini M, Goffredo L, Bertoletti A, Klersy C, Pecci A, Moratti R, Tavazzi L (2005) Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood 105:199–206

    Article  CAS  PubMed  Google Scholar 

  33. Turan RG, Brehm M, Koestering M, Tobias Z, Bartsch T, Steiner S, Picard F, Ebner P, Schannwell CM, Strauer BE (2007) Factors influencing spontaneous mobilization of CD34+ and CD133+ progenitor cells after myocardial infarction. Eur J Clin Invest 37:842–851

    Article  CAS  PubMed  Google Scholar 

  34. Grundmann F, Scheid C, Braun D, Zobel C, Reuter H, Schwinger RH, Müller-Ehmsen J (2007) Differential increase of CD34, KDR/CD34, CD133/CD34 and CD117/CD34 positive cells in peripheral blood of patients with acute myocardial infarction. Clin Res Cardiol 96:621–627

    Article  CAS  PubMed  Google Scholar 

  35. Ozaki Y, Nishimura M, Sekiya K, Suehiro F, Kanawa M, Nikawa H, Hamada T, Kato Y (2007) Comprehensive analysis of chemotactic factors for bone marrow mesenchymal stem cells. Stem Cells Dev 16:119–129

    Article  CAS  PubMed  Google Scholar 

  36. Croitoru-Lamoury J, Lamoury FM, Zaunders JJ, Veas LA, Brew BJ (2007) Human mesenchymal stem cells constitutively express chemokines and chemokine receptors that can be upregulated by cytokines, IFN-beta, and Copaxone. J Interferon Cytokine Res 27:53–64

    Article  CAS  PubMed  Google Scholar 

  37. Ries C, Egea V, Karow M, Kolb H, Jochum M, Neth P (2007) MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood 109:4055–4063

    Article  CAS  PubMed  Google Scholar 

  38. Ben-Tal Cohen E, Hohensinner PJ, Kaun C, Maurer G, Huber K, Wojta J (2007) Statins decrease TNF-alpha-induced osteoprotegerin production by endothelial cells and smooth muscle cells in vitro. Biochem Pharmacol 73:77–83

    Article  CAS  PubMed  Google Scholar 

  39. Lee RH, Seo MJ, Pulin AA, Gregory CA, Ylostalo J, Prockop DJ (2009) The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice. Blood 113:816–826

    Article  CAS  PubMed  Google Scholar 

  40. Guo J, Lin GS, Bao CY, Hu ZM, Hu MY (2007) Anti-inflammation role for mesenchymal stem cells transplantation in myocardial infarction. Inflammation 30:97–104

    Article  CAS  PubMed  Google Scholar 

  41. Zauli G, Pandolfi A, Gonelli A, Di Pietro R, Guarnieri S, Ciabattoni G, Rana R, Vitale M, Secchiero P (2003) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sequentially up-regulates nitric oxide and prostanoid production in primary human endothelial cells. Circ Res 92:732–740

    Article  CAS  PubMed  Google Scholar 

  42. Secchiero P, Corallini F, di Iasio MG, Gonelli A, Barbarotto E, Zauli G (2005) TRAIL counteracts the proadhesive activity of inflammatory cytokines in endothelial cells by down-modulating CCL8 and CXCL10 chemokine expression and release. Blood 105:3413–3419

    Article  CAS  PubMed  Google Scholar 

  43. Secchiero P, Candido R, Corallini F, Zacchigna S, Toffoli B, Rimondi E, Fabris B, Giacca M, Zauli G (2006) Systemic TRAIL delivery shows anti-atherosclerotic activity in apoE-null diabetic mice. Circulation 114:1522–1530

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by a grant from “Programma di Ricerca Regione-Università 2007/2009” (Regione Emilia Romagna) to R.F. and P.S.

Author information

Authors and Affiliations

  1. Department of Morphology and Embryology, University of Ferrara, Via Fossato di Mortara 66, 44100, Ferrara, Italy

    Federica Corallini, Paola Secchiero & Giorgio Zauli

  2. Interdepartmental Center of Regenerative Medicine, University of Udine, Udine, Italy

    Antonio Paolo Beltrami, Daniela Cesselli, Elisa Puppato & Carlo Alberto Beltrami

  3. Cardiovascular Institute, Azienda Ospedaliera-Universitaria S. Anna, Ferrara, Italy

    Roberto Ferrari

Authors
  1. Federica Corallini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paola Secchiero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonio Paolo Beltrami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniela Cesselli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elisa Puppato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roberto Ferrari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carlo Alberto Beltrami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giorgio Zauli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giorgio Zauli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Corallini, F., Secchiero, P., Beltrami, A.P. et al. TNF-α modulates the migratory response of mesenchymal stem cells to TRAIL. Cell. Mol. Life Sci. 67, 1307–1314 (2010). https://doi.org/10.1007/s00018-009-0246-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-009-0246-5

Keywords

Search

Navigation