Skip to main content
SpringerLink
Log in

Regenerative Therapien für Kinderherzen

Regenerative therapies for congenital heart disease

  • Stand der Wissenschaft
  • Published:
Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Die chirurgische Korrektur kongenitaler Herzfehler kann heute mit exzellenten Resultaten durchgeführt werden. Postoperative, chronische kardiale Belastungszustände sind insbesondere bei komplexen Anomalien nicht immer vermeidbar. Regenerative Therapiekonzepte stellen zur komplementären Behandlung kongenitaler Herzfehler eine aussichtsreiche Option dar. In unseren Arbeiten wurden in zwei experimentellen Modellen an Lämmern zur Druck- und Volumenbelastung der rechten Herzkammer jeweils autologe, mononukleäre Nabelschnurblutzellen und Erythropoietin eingesetzt. Die Effekte der intramyokardial applizierten mononukleären Zellen im Volumenbelastungsmodell scheinen in erster Linie in einer Verbesserung der diastolischen rechtsventrikulären Funktion nach 3 Monaten durch eine Erhöhung der Kapillardichte zu bestehen. Intramyokardial und systemisch verabreichtes Erythropoietin hat nach unseren Ergebnissen einen positiven Einfluss auf Kapillardichte, Fibrosegrad und Proliferationsrate des Herzmuskels. Weiterhin fanden wir eine niedrigere Aktivität von myokardialen Proteinen, welche die Apoptoseaktivität und die Inflammation triggern. Die Elastizität des chronisch druckbelasteten rechten Ventrikels war nach 3 Monaten in der Behandlungsgruppe signifikant besser. Diese Daten stützen das Potenzial regenerativer Therapien in der komplementären Behandlung angeborener Herzfehler.

Abstract

Nowadays surgical treatment of congenital heart disease can be performed with excellent outcome. However, chronic postoperative cardiac overload cannot always be obviated especially with more complex anomalies. Therefore, regenerative therapeutic concepts may offer promising options for complementary management of congenital heart disease. In this study umbilical cord blood mononuclear cells and erythropoietin were employed in two different models for volume and pressure overload of the right ventricle, respectively. Enhancement of myocardial capillary density seems to be the most significant effect of the intramyocardial application of umbilical cord mononuclear cells for a significant improvement of diastolic properties of the right ventricle after 3 months chronic volume overload. Erythropoietin, which was administered via an intramyocardial and systemic route, has positive effects by enhancing capillary density, limiting fibrosis and augmenting proliferation activity of the myocardium. In addition lower apoptosis and inflammation could be observed at the level of myocardial protein expression. Hence, the elasticity of the chronically pressure overloaded ventricle was superior with erythropoietin treatment than in the control group 3 months postoperatively. These data support the potential of regenerative therapies in the complementary therapy of congenital heart disease.

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

Abb. 1

Literatur

  1. Bohlius J, Weingart O, Trelle S, Engert A (2006) Cancer-related anemia and recombinant human erythropoietin – an updated overview. Nat Clin Pract Oncol 3:152–164

    Article  PubMed  CAS  Google Scholar 

  2. Bonanno G, Mariotti A, Procoli A et al (2007) Human cord blood CD133+ cells immunoselected by a clinical-grade apparatus differentiate in vitro into endothelial- and cardiomyocyte-like cells. Transfusion 47:280–289

    Article  PubMed  CAS  Google Scholar 

  3. Calvillo L, Latini R, Kajstura J et al (2003) Recombinant human erythropoietin protects the myocardium from ischemia- reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci U S A 100:4802–4806

    Article  PubMed  CAS  Google Scholar 

  4. Chen LL, Yin H, Huang J (2007) Inhibition of TGF-beta1 signaling by eNOS gene transfer improves ventricular remodeling after myocardial infarction through angiogenesis and reduction of apoptosis. Cardiovasc Pathol 16:221–230

    Article  PubMed  CAS  Google Scholar 

  5. Condorelli G, Morisco C, Stassi G et al (1999) Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat. Circulation 99:3071–3078

    PubMed  CAS  Google Scholar 

  6. Fan CL, Li Y, Gao PJ et al (2003) Differentiation of endothelial progenitor cells from human umbilical cord blood CD 34+ cells in vitro. Acta Pharmacol Sin 24:212–218

    PubMed  CAS  Google Scholar 

  7. Flores AI, McKenna DH, Montalban MA et al (2009) Consistency of the initial cell acquisition procedure is critical to the standardization of CD34+ cell enumeration by flow cytometry: results of a pairwise analysis of umbilical cord blood units and cryopreserved aliquots. Transfusion 49:636–647

    Article  PubMed  Google Scholar 

  8. Friehs I, Moran AM, Stamm C et al (2004) Promoting angiogenesis protects severely hypertrophied hearts from ischemic injury. Ann Thorac Surg 77:2004–2010; discussion 2011

    Article  PubMed  Google Scholar 

  9. Fu P, Arcasoy MO (2007) Erythropoietin protects cardiac myocytes against anthracycline-induced apoptosis. Biochem Biophys Res Commun 354:372–378

    Article  PubMed  CAS  Google Scholar 

  10. Fukuda S, Kaga S, Zhan L et al (2006) Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1. Cell Biochem Biophys 44:43–49

    Article  PubMed  CAS  Google Scholar 

  11. Gluckman E, Broxmeyer HA, Auerbach AD et al (1989) Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med 321:1174–1178

    Article  PubMed  CAS  Google Scholar 

  12. Hare JM, Chaparro SV (2008) Cardiac regeneration and stem cell therapy. Curr Opin Organ Transplant 13:536–542

    Article  PubMed  Google Scholar 

  13. Hu CH, Li ZM, Du ZM et al (2009) Human umbilical cord-derived endothelial progenitor cells promote growth cytokines-mediated neorevascularization in rat myocardial infarction. Chin Med J (Engl) 122:548–555

    Google Scholar 

  14. Jackson KA, Majka SM, Wang H et al (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107:1395–1402

    Article  PubMed  CAS  Google Scholar 

  15. Kern S, Eichler H, Stoeve J et al (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24:1294–1301

    Article  PubMed  CAS  Google Scholar 

  16. Klopsch C, Furlani D, Gabel R et al (2009) Intracardiac injection of erythropoietin induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model. J Cell Mol Med 13:664–679

    Article  PubMed  CAS  Google Scholar 

  17. Kogler G, Sensken S, Airey JA et al (2004) A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 200:123–135

    Article  PubMed  Google Scholar 

  18. Liu X, Shen J, Jin Y et al (2006) Recombinant human erythropoietin (rhEPO) preconditioning on nuclear factor-kappa B (NF-kB) activation & proinflammatory cytokines induced by myocardial ischaemia-reperfusion. Indian J Med Res 124:343–354

    PubMed  CAS  Google Scholar 

  19. Nishiya D, Omura T, Shimada K et al (2006) Effects of erythropoietin on cardiac remodeling after myocardial infarction. J Pharmacol Sci 101:31–39

    Article  PubMed  CAS  Google Scholar 

  20. Rui T, Feng Q, Lei M et al (2005) Erythropoietin prevents the acute myocardial inflammatory response induced by ischemia/reperfusion via induction of AP-1. Cardiovasc Res 65:719–727

    Article  PubMed  CAS  Google Scholar 

  21. Stamm C, Kleine HD, Choi YH et al (2007) Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J Thorac Cardiovasc Surg 133:717–725

    Article  PubMed  Google Scholar 

  22. Strauer BE, Brehm M, Zeus T et al (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913–1918

    Article  PubMed  Google Scholar 

  23. Van der Meer P, Lipsic E, Henning RH et al (2005) Erythropoietin induces neovascularization and improves cardiac function in rats with heart failure after myocardial infarction. J Am Coll Cardiol 46:125–133

    Article  Google Scholar 

  24. Yerebakan C, Klopsch C, Niefeldt S et al (2010) Acute and chronic response of the right ventricle to surgically induced pressure and volume overload – An analysis of pressure-volume relations. Interact Cardiovasc Thorac Surg 10:519–525

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt

Der Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Cardiovascular Surgery, Children’s National Medical Center, Children’s National Heart Institute, 111 Michigan Avenue, 20010, Washington, D.C., USA

    C. Yerebakan

  2. Abteilung für Herzchirurgie, Universitäres Herzzentrum Rostock, Rostock, Deutschland

    S. Niefeldt, C. Klopsch, S. Prietz & G. Steinhoff

  3. Fachbereich Molekularbiologie, Leibniz-Institut für Nutztierbiologie, Dummerstorf, Deutschland

    A. Rebl & T. Goldammer

  4. Abteilung Zelltherapie, Fraunhofer Institut für Zelltherapie und Immunologie, Leipzig, Deutschland

    J. Boltze

  5. Translationszentrum für Regenerative Medizin, Leipzig, Deutschland

    J. Boltze

  6. Abt. für Chirurgie Angeborener Herzfehler, Herz- und Diabeteszentrum NRW, Bad Oeynhausen, Deutschland

    E. Sandica

Authors
  1. C. Yerebakan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Niefeldt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Klopsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Prietz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Rebl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. Goldammer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Boltze
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. Sandica
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G. Steinhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Yerebakan.

Zusatzmaterial online

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yerebakan, C., Niefeldt, S., Klopsch, C. et al. Regenerative Therapien für Kinderherzen. Z Herz- Thorax- Gefäßchir 25, 235–240 (2011). https://doi.org/10.1007/s00398-011-0862-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00398-011-0862-x

Schlüsselwörter

Keywords

Search

Navigation