cArbeitsgruppe | Dr. Tongers

Research Focus

Ischemic tissue repair
Despite continuous medical progress, the burden of ischemic cardiovascular disease is growing. Therefore, therapeutic strategies to repair ischemic tissue have been developed, e.g. gene therapy, stem cell-based therapy, tissue/bioengineering. In this context, adult stem cells have been emerging as a promising therapeutic option, although early clinical trials have generated mixed results. So far, uncertainties and limitations impair the efficacy of cell-based therapy. We are interested to further understand mechanism of cell-based tissue repair, analyze factors that influence regenerative benefit, and develop strategies to enhance the potency of cell-based therapy.

 

Biomaterials for cardiovascular applications

In the evolving field of biotechnology, a variety of biomaterials has recently been developed for medical use, including particles, fibers, scaffolds, and matrices. This technology allows to specifically design biomaterials for therapeutic applications. Herein, structure, dimensions, and shape of constructs are pivotal to mimic the native tissue architecture; 3-dimensionality enhances biological cell-cell and cell-matrix interaction. Ideally, biomatrices additionally incorporate bioactive signals to specifically target biology. The nanofiber system we have been using is structurally based on peptide amphiphiles (PA), self-assembles into a 3-dimensional network after simple injection, allows to incorporate bioactive epitopes or binding groups, and biodegrades into harmless byproducts. Our results show, for example, that specifically designed PA nanofibers are capable of enhancing cell-based therapy.

 

Role of the hemeoxygenase system in cardiovascular disease

The hemeoxygenase (HO) enzyme family has been characterized as a central molecule of endogenous protection and adaptation in pathologic states, conferring anti-apoptotic, anti-inflammatory, anti-oxidative, and pro-angiogenic properties. Functionally, the HO system catalyzes the cleavage of heme into carbon monoxide (CO), biliverdin (BV), which is transferred into bilirubin (BR), and ferrous iron. Opposed to the constitutive isoforms (HO-2, HO-3), hemeoxygenase-1 (HO-1) is strongly inducible upon pathologic states, such as hypoxia/ischemia, oxidative stress, and inflammation, and is the rate-limiting enzyme of heme degradation. Our interest is to characterize its role in preclinical cardiovascular disease models, and to evaluate its clinical potential.

Publications
  • Tongers J, Roncalli JG, Losordo DW. Role of Endothelial Progenitor Cells During Ischemia-induced Vasculogenesis and Collateral Formation. Microvasc. Res. 2010 (in press).

  • Webber MJ*, Tongers J*, Renault MA, Roncalli JG, Losordo DW, Stupp SI. Development of Bioactive Peptide Amphiphiles for Therapeutic Cell Delivery  Acta Biomater. 2010; 6: 3-11.

  • Gupta R, Tongers J, Losordo DW. Human Studies of Angiogenic Gene Therapy. Circ. Res. 2009; 105: 724-736.

  • Tongers J, Webber MJ, Losordo DW. Bioengineering to Enhance Progenitor Cell Therapeutics. Tex. Heart Inst. J. 2009; 36:140-144.

  • Renault MA, Roncalli J, Tongers J, Misener S, Thorne T, Jujo K, Ito A, Clark T, Fung C, Millay M, Kamide C, Scarpelli A, Klyachko E, Losordo DW. The Hedgehog Transcription Factor Gli3 Modulates Angiogenesis. Circ. Res. 2009; 105: 818-826.

  • Tongers J, Roncalli JG, Losordo DW. Cardiovascular Gene Therapy. In: Templeton NS, ed. Gene and Cell Therapy: Therapeutic Mechanisms and Strategies. 3rd ed. Boca Raton: CRC Press; 2009: 975-999.

  • Tongers J, Roncalli JG, Losordo DW. Therapeutic Angiogenesis for Critical Limb Ischemia: Microvascular Therapies Coming of Age. Circulation 2008; 118: 9-16.

  • Roncalli JG*, Tongers J*, Renault M-A, Losordo DW. Biological Approaches to Ischemic Tissue Repair: Gene- and Cell-based Strategies. Exp. Rev. Cardiovasc. Ther. 2008; 6: 653-668.

  • Tongers J, Knapp J-M, Korf M, Kempf T, Limbourg A, Limbourg FP, Li Z, Fraccarollo D, Bauersachs J, Han X, Drexler H, Fiedler B, Wollert KC. Haeme Oxygenase Promotes Progenitor Cell Mobilization, Neovascularization, and Functional Recovery after Critical Hindlimb Ischaemia in Mice. Cardiovasc. Res. 2008; 78: 294-300.

  • Roncalli JG, Tongers J, Renault M-A, Losordo DW. Endothelial Progenitor Cells in Regenerative medicine and Cancer: a Decade of Research. Trends Biotechnol. 2008; 26: 276-283.

  • Tongers J, Losordo DW. Frontiers in Nephrology: the Evolving Therapeutic Applications of Endothelial Progenitor cells. J. Am. Soc. Nephrol. 2007, 18: 2843-2852.

  • Tongers J, Schwerdtfeger B, Klein G, Kempf T, Schaefer A, Knapp J-M, Niehaus M, Korte T, Hoeper MM. Incidence and Clinical Relevance of Supraventricular Tachyarrhythmias in Pulmonary Hypertension. Am. Heart J. 2007; 153: 127-132.

  • Tongers J, Fiedler B, König D, Kempf T, Klein G, Heineke J, Kraft T, Gambaryan S, Lohmann SM, Drexler H, Wollert KC. – Heme Oxygenase-1 Inhibition of MAP Kinases, Calcineurin/NFAT Signaling, and Hypertrophy in Cardiac Myocytes. Cardiovasc. Res. 2004; 63: 545-552.

Collaborations
  • Prof. Douglas W. Losordo, Feinberg Cardiovascular Research Institute and Program in Cardiovascular Regenerative Medicine, Northwestern University, Chicago, USA
  • Prof. Samuel I. Stupp, Institute for BioNanotechnology in Medicine, Northwestern University, Evanston, USA
Support
  • Ernest-Solvay-Foundation, Start-up Funding
  • Hannover Medical School, Young Investigator Early Career Grant (HiLF Program)
  • Baxter, Baxter-Northwestern Alliance

Group leader

Dr. Jörn Tongers
Tel.: 0511 532-4059 
Fax: 0511 532-3357
tongers.joern@mh-hannover.de

Kardiologisches Forschungslabor
Gebäude I3
Ebene SO
Raum 2290

Tel: | 0511 532-5773
Fax: 0511 532-8194

Members

Katja-Theres Marquardt
Medical student, doctoral candidate
katja-theres.marquardt@stud.mh-hannover.de

Roberto Giagnorio
Medical student, doctoral candidate
roberto.giagnorio@stud.mh-hannover.de

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