Log in

Biological pacing by gene and cell therapy

  • Interuniversity Cardiology Institute of the Netherlands
  • Published:
Netherlands Heart Journal Aims and scope Submit manuscript

Abstract

At present, cardiac rhythm disorders such as sick sinus syndrome (SSS) or AV nodal block (AVB) are usually treated by electronic pacemakers. These devices have significant shortcomings, including lack of autonomic modulation, and the need for repetitive procedures for battery replacement or lead repositioning. Biological pacemakers as replacement or complement to electronic pacemakers have been the subject of increasing research interest. This research has resulted in many encouraging preclinical studies. Various approaches in the field of gene and cell therapy have been developed by different groups and this combined effort makes it increasingly realistic that this therapy will eventually find its way to clinical applicability. (Neth Heart J 2007;15:318-22.)

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Verkerk AO, Wilders R, van Borren MM, Peters RJ, Broekhuis E, Lam K, et al. Pacemaker current (If) in the human sinoatrial node. Eur Heart J. In press 2007.

  • Mistrik P, Mader R, Michalakis S, Weidinger M, Pfeifer A, Biel M. The murine HCN3 gene encodes a hyperpolarization-activated cation channel with slow kinetics and unique response to cyclic nucleotides. J Biol Chem 2005;280:27056-61.

    Google Scholar 

  • Seifert R, Scholten A, Gauss R, Mincheva A, Lichter P, Kaupp UB. Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis. Proc Natl Acad Sci USA 1999;96:9391-6.

    Google Scholar 

  • Shi W, Wymore R, Yu H, Wu J, Wymore RT, Pan Z, et al. Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissues. Circ Res 1999;85:e1-e6.

    Google Scholar 

  • DiFrancesco D. Cardiac pacemaker I(f) current and its inhibition by heart rate-reducing agents. Curr Med Res Opin 2005;21:1115-22.

    Google Scholar 

  • Rosen MR, Brink PR, Cohen IS, Robinson RB. Genes, stem cells and biological pacemakers. Cardiovasc Res 2004;64:12-23.

    Google Scholar 

  • Miake J, Marbán E, Nuss HB. Functional role of inward rectifier current in heart probed by Kir2.1 overexpression and dominant-negative suppression. J Clin Invest 2003;111:1529-36.

    Google Scholar 

  • Miake J, Marbán E, Nuss HB. Biological pacemaker created by gene transfer. Nature 2002;419:132-3.

    Google Scholar 

  • Tan HL, Hou CJ, Lauer MR, Sung RJ. Electrophysiologic mechanisms of the long QT interval syndromes and torsade de pointes. Ann Intern Med 1995;122:701-14.

    Google Scholar 

  • Tristani-Firouzi M, Jensen JL, Donaldson MR, Sansone V, Meola G, Hahn A, et al. R. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest 2002;110: 381-8.

  • Zhang L, Benson DW, Tristani-Firouzi M, Ptacek LJ, Tawil R, Schwartz PJ, et al. Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic T-U-wave patterns predict the KCNJ2 genotype. Circulation 2005;111:2720-6.

    Google Scholar 

  • Qu J, Barbuti A, Protas L, Santoro B, Cohen IS, Robinson RB. HCN2 overexpression in newborn and adult ventricular myocytes: distinct effects on gating and excitability. Circ Res 2001;89:E8-14.

    Google Scholar 

  • Qu J, Plotnikov AN, Danilo P Jr, Shlapakova I, Cohen IS, Robinson RB, et al. Expression and function of a biological pacemaker in canine heart. Circulation 2003;107:1106-9.

    Google Scholar 

  • Bucchi A, Plotnikov AN, Shlapakova I, Danilo P Jr., Kryukova Y, Qu J, et al. Wild-type and mutant HCN channels in a tandem biological-electronic cardiac pacemaker. Circulation 2006;114:992-9.

    Google Scholar 

  • Tse HF, Xue T, Lau CP, Siu CW, Wang K, Zhang QY, et al. Bioartificial sinus node constructed via in vivo gene transfer of an engineered pacemaker HCN Channel reduces the dependence on electronic pacemaker in a sick-sinus syndrome model. Circulation 2006;114:1000-11.

    Google Scholar 

  • Borer JS. Drug insight: If inhibitors as specific heart-rate-reducing agents. Nat Clin Pract Cardiovasc Med 2004;1:103-9.

    Google Scholar 

  • DiFrancesco D. Cardiac pacemaker I(f) current and its inhibition by heart rate-reducing agents. Curr Med Res Opin 2005;21:1115-22.

    Google Scholar 

  • Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, et al. Human mesenchymal stem cells engraft and demonstrate sitespecific differentiation after in utero transplantation in sheep. Nat Med 2000;6:1282-6.

    Google Scholar 

  • Kehat I, Khimovich L, Caspi O, Gepstein A, Shofti R, Arbel G, et al. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol 2004;22:1282-9.

    Google Scholar 

  • Xue T, Cho HC, Akar FG, Tsang SY, Jones SP, Marban E, et al. Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers. Circulation 2005;111:11-20.

    Google Scholar 

  • Srivastava D, Ivey KN. Potential of stem-cell-based therapies for heart disease. Nature 2006;441:1097-9.

    Google Scholar 

  • Rosen MR. 15th annual Gordon K. Moe Lecture. Biological pacemaking: in our lifetime? Heart Rhythm 2005;2:418-28.

    Google Scholar 

  • Potapova I, Plotnikov A, Lu Z, Danilo P Jr, Valiunas V, Qu J, et al. Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers. Circ Res 2004;94:952-9.

    Google Scholar 

  • Robinson RB, Rosen MR, Brink PR, Cohen IS. Letter regarding the article by Xue et al, “Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes”. Circulation 2005;112:e82-e83.

    Google Scholar 

  • Fleury S, Simeoni E, Zup**er C, Déglon N, von Segesser LK, Kappenberger L, et al. Multiply attenuated, self-inactivating lentiviral vectors efficiently deliver and express genes for extended periods of time in adult rat cardiomyocytes in vivo. Circulation 2003;107:2375-82.

    Google Scholar 

  • Seppen J, Barry SC, Harder B, Osborne WRA. Lentivirus administration to rat muscle provides efficient sustained expression of erythropoietin. Blood 2001;98:594-6.

    Google Scholar 

  • Seppen J, van Til NP, van der Rijt R, Hiralall JK, Kunne C, Oude Elferink RPJ. Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats. Gene Ther 2006;13:672-7.

    Google Scholar 

  • Pacak CA, Mah CS, Thattaliyath BD, Conlon TJ, Lewis MA, Cloutier DE, et al. Recombinant adeno-associated virus serotype 9 leads to preferential cardiac transduction in vivo. Circ Res 2006; 99:e3-e9.

    Google Scholar 

  • Rosen AB, Kelly DJ, Schuldt AJ, Lu J, Potapova IA, Doronin SV, et al. Finding Fluorescent Needles in the Cardiac Haystack: Tracking Human Mesenchymal Stem Cells Labeled with Quantum Dots for Quantitative In Vivo 3-D Fluorescence Analysis. Stem Cells 2007 May 10 (Epub ahead of print).

  • Boink GJJ, Verkerk AO, van Amersfoorth SC, Tasseron S, van der Meulen J, de Bakker JMT, et al. Increased spontaneous activity and autonomic modulation in lentiviral transduced rat cardiac myocytes overexpressing HCN4. Heart Rhythm 2007 (meeting abstract).

  • Biel M, Schneider A, Wahl C. Cardiac HCN channels: structure, function, and modulation. Trends Cardiovasc Med 2002;12:206-12.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Heart Failure Research Centre, Academic Medical Centre, University of Amsterdam, Amsterdam, and Interuniversity Cardiology Institute Netherlands, Utrecht, the Netherlands

Heart Failure Research Centre, and Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands

H.L. Tan Department of Clinical and Experimental Cardiology, Heart Failure Research Centre, Academic Medical Centre, PO Box 22660, 1100 DD Amsterdam, the Netherlands

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boink, G.J.J., Seppen, J., de Bakker, J.M.T. et al. Biological pacing by gene and cell therapy. NHJL 15, 318–322 (2007). https://doi.org/10.1007/BF03086008

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03086008

Navigation