Large Animal Models for Myocardial Repair

Objectives

We aim to implement an appropriate animal models for myocardial replacement and regeneration using tissue engineeringand cell therapy approaches.

Our long term goals is to develop an in vivo replacement of diseased myocardium using tissue engineered beating myocardial patch with immediate improve of cardiac function.

Research Focus

The aim is to establish large animal models to test myocardial tissue engineered constructs and their remodelling in vivo. For these purposes a myocardial infarction model should be established. Surgical implantations of tissue engineered myocardial constructs, but also implantation of autologous or allo-, xenogenic decellularized tissue in order to induce guided tissue regeneration are planned. Implementation of different anti-rejection protocols should be performed according to the nature of implanted tissue. As end-points in vivo tissue remodelling, tissue integration as well as tissue function should be investigated using different histological, imagistic and functional methods of investigation. These experiments should be compared to in vivo remodelling of tissue engineered grafts implanted in healthy (non-infarction) animals.

Collaborations

Publications

2013 - ongoing

2017

Shrestha ML, Beckmann E, Abd Alhadi F, Krueger H, Meyer-Bockenkamp F, Bertele S, Koigeldiyev N, Kaufeld T, Fleissner F, Korte W, Schmitto J, Cebotari S, Harringer W, Haverich A, Martens A. Elective David I Procedure Has Excellent Long-Term Results: 20-Year Single-Center Experience. Ann Thorac Surg. 2017. Epub 2017/12/05.

Goecke T, Theodoridis K, Tudorache I, Ciubotaru A, Cebotari S, Ramm R, Hoffler K, Sarikouch S, Vasquez-Rivera A, Haverich A, Wolkers WF, Hilfiker A. In vivo performance of freeze-dried decellularized pulmonary heart valve allo- and xenografts orthotopically implanted into juvenile sheep. Acta Biomater. 2017/12/02 ed2017.

Ius F, Haverich A, Cebotari S. Reply to Hernandez-Vaquero et al. Eur J Cardiothorac Surg. 2017. Epub 2017/11/22.

Madrahimov N, Natanov R, Boyle EC, Goecke T, Knofel AK, Irkha V, Solovieva A, Hoffler K, Maus U, Kuhn C, Ismail I, Warnecke G, Shrestha ML, Cebotari S, Haverich A. Cardiopulmonary Bypass in a Mouse Model: A Novel Approach. J Vis Exp. 2017(127). Epub 2017/10/11.

Madrahimov N, Boyle EC, Gueler F, Goecke T, Knofel AK, Irkha V, Maegel L, Hoffler K, Natanov R, Ismail I, Maus U, Kuhn C, Warnecke G, Shrestha ML, Cebotari S, Haverich A. Novel mouse model of cardiopulmonary bypass. Eur J Cardiothorac Surg. 2018;53(1):186-93. Epub 2017/10/05.

Shrestha M, Martens A, Kaufeld T, Beckmann E, Bertele S, Krueger H, Neuser J, Fleissner F, Ius F, Abd Alhadi F, Hanke J, Schmitto JD, Cebotari S, Karck M, Haverich A, Chavan A. Single-centre experience with the frozen elephant trunk technique in 251 patients over 15 years. Eur J Cardiothorac Surg. 2017;52(5):858-66. Epub 2017/10/05.

Theodoridis K, Tudorache I, Cebotari S, Calistru A, Meyer T, Sarikouch S, Bara C, Haverich A, Hilfiker A. Six-Year-Old Sheep as a Clinically Relevant Large Animal Model for Aortic Valve Replacement Using Tissue-Engineered Grafts Based on Decellularized Allogenic Matrix. Tissue Eng Part C Methods. 2017/09/20 ed2017.

Beckmann E, Martens A, Pertz J, Kaufeld T, Umminger J, Hanke JS, Schmitto JD, Cebotari S, Haverich A, Shrestha ML. Valve-sparing David I procedure in acute aortic type A dissection: a 20-year experience with more than 100 patients. Eur J Cardiothorac Surg. 2017;52(2):319-24. Epub 2017/08/26.

Ius F, Schulz J, Roumieh M, Fleissner F, Ismail I, Tudorache I, Warnecke G, Martens A, Shrestha M, Boethig D, Haverich A, Cebotari S. Long-term results of the Mitroflow aortic pericardial bioprosthesis in over 800 patients: limited durability and mechanisms of dysfunction. Eur J Cardiothorac Surg. 2017;52(2):264-71. Epub 2017/08/26.

Braniste T, Tiginyanu I, Horvath T, Raevschi S, Andree B, Cebotari S, Boyle EC, Haverich A, Hilfiker A. Targeting Endothelial Cells with Multifunctional GaN/Fe Nanoparticles. Nanoscale Res Lett. 2017/08/12 ed2017. p. 486.

Mogaldea A, Goecke T, Theodoridis K, Haverich A, Cebotari S, Hilfiker A. Tissue Engineering of Vein Valves Based on Decellularized Natural Matrices. Cells Tissues Organs. 2017;204(3-4):199-209. Epub 2017/08/09.

Olsson KM, Wiedenroth CB, Kamp JC, Breithecker A, Fuge J, Krombach GA, Haas M, Hamm C, Kramm T, Guth S, Ghofrani HA, Hinrichs JB, Cebotari S, Meyer K, Hoeper MM, Mayer E, Liebetrau C, Meyer BC. Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension: the initial German experience. Eur Respir J. 2017;49(6). Epub 2017/06/10.

Sarikouch S, Haverich A, Pepper J, Pomar JL, Hazekamp M, Padalino M, Stellin G, Meyns B, Laufer G, Andreas M, Hubler M, Schmiady M, Ciubotaru A, Horke A, Cebotari S, Tudorache I. Every like is not the same. J Thorac Cardiovasc Surg. 2017;153(6):1553-5. Epub 2017/05/21.

David S, Hoeper MM, Vogel-Claussen J, Cebotari S. Pulmonary Arterial Sarcoma Presenting as Acute Pulmonary Embolism. Am J Respir Crit Care Med. 2017;196(4):523. Epub 2017/05/16.

Beckmann E, Ismail I, Cebotari S, Busse A, Martens A, Shrestha M, Kuhn C, Haverich A, Fegbeutel C. Right-Sided Heart Failure and Extracorporeal Life Support in Patients Undergoing Pericardiectomy for Constrictive Pericarditis: A Risk Factor Analysis for Adverse Outcome. Thorac Cardiovasc Surg. 2017;65(8):662-70. Epub 2016/11/18.

Rojas SV, Meier M, Zweigerdt R, Eckardt D, Rathert C, Schecker N, Schmitto JD, Rojas-Hernandez S, Martin U, Kutschka I, Haverich A, Martens A. Multimodal Imaging for In Vivo Evaluation of Induced Pluripotent Stem Cells in a Murine Model of Heart Failure. Artificial organs. 2017;41(2):192-9.

Fleissner F, Issam I, Martens A, Cebotari S, Haverich A, Shrestha ML. The Unplanned Postoperative Coronary Angiogram after CABG: Identifying the Patients at Risk. Thorac Cardiovasc Surg. 2017;65(4):292-5. Epub 2015/10/31.

2016

Tudorache I, Theodoridis K, Baraki H, Sarikouch S, Bara C, Meyer T, Hoffler K, Hartung D, Hilfiker A, Haverich A, Cebotari S. Decellularized aortic allografts versus pulmonary autografts for aortic valve replacement in the growing sheep model: haemodynamic and morphological results at 20 months after implantation. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2016;49(4):1228-38.

Tudorache I, Horke A, Cebotari S, Sarikouch S, Boethig D, Breymann T, Beerbaum P, Bertram H, Westhoff-Bleck M, Theodoridis K, Bobylev D, Cheptanaru E, Ciubotaru A, Haverich A. Decellularized aortic homografts for aortic valve and aorta ascendens replacement. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2016;50(1):89-97.

Sarikouch S, Horke A, Tudorache I, Beerbaum P, Westhoff-Bleck M, Boethig D, Repin O, Maniuc L, Ciubotaru A, Haverich A, Cebotari S. Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2016;50(2):281-90.

Martens A, Beckmann E, Kaufeld T, Umminger J, Fleissner F, Koigeldiyev N, Krueger H, Puntigam J, Haverich A, Shrestha M. Total aortic arch repair: risk factor analysis and follow-up in 199 patients. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2016;50(5):940-8.

2015

Theodoridis K, Tudorache I, Calistru A, Cebotari S, Meyer T, Sarikouch S, Bara C, Brehm R, Haverich A, Hilfiker A. Successful matrix guided tissue regeneration of decellularized pulmonary heart valve allografts in elderly sheep. Biomaterials. 2015;52:221-8.

Iablonskii P, Cebotari S, Tudorache I, Granados M, Morticelli L, Goecke T, Klein N, Korossis S, Hilfiker A, Haverich A. Tissue-engineered mitral valve: morphology and biomechanics dagger. Interact Cardiovasc Thorac Surg. 2015;20(6):712-9; discussion 9.

Goecke T, Hilfiker A, Haverich A, Cebotari S. Investigation of inflammatory response of decellularized porcine aortic tissue in mice: can we rely on this experimental setting? European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2015;47(3):e90-1.

Roumieh M, Ius F, Tudorache I, Ismail I, Fleissner F, Haverich A, Cebotari S. Comparison between Biological and Mechanical Aortic Valve Prostheses in Middle-Aged Patients Matched through Propensity Score Analysis: Long-Term Results. Eur J Cardiothorac Surg. 2015;48(1):129-36.

Tudorache I, Theodoridis K, Baraki H, Sarikouch S, Bara C, Meyer T, Hoffler K, Hartung D, Hilfiker A, Haverich A, Cebotari S. Decellularized Aortic Allografts Versus Pulmonary Autografts for Aortic Valve Replacement in the Growing Sheep Model: Haemodynamic and Morphological Results at 20 Months after Implantation. Eur J Cardiothorac Surg. 2015.

Goecke T, Hilfiker A, Haverich A, Cebotari S. Investigation of Inflammatory Response of Decellularized Porcine Aortic Tissue in Mice: Can We Rely on This Experimental Setting? Eur J Cardiothorac Surg. 2015;47(3):e90-1.

Goecke T, Tudorache I, Hilfiker A, Haverich A, Cebotari S. [Prefabrication of Heart Valves]. Chirurg. 2015;86(3):251-3. Prafabrikation von Herzklappen.

Iablonskii P, Cebotari S, Tudorache I, Granados M, Morticelli L, Goecke T, Klein N, Korossis S, Hilfiker A, Haverich A. Tissue-Engineered Mitral Valve: Morphology and Biomechanics Dagger. Interact Cardiovasc Thorac Surg. 2015;20(6):712-9; discussion 9.

2014

Neumann A, Sarikouch S, Breymann T, Cebotari S, Boethig D, Horke A, Beerbaum P, Westhoff-Bleck M, Bertram H, Ono M, Tudorache I, Haverich A, Beutel G. Early Systemic Cellular Immune Response in Children and Young Adults Receiving Decellularized Fresh Allografts for Pulmonary Valve Replacement. Tissue Eng Part A. 2014;20(5-6):1003-11.

Vukadinovic-Nikolic Z, Andree B, Dorfman SE, Pflaum M, Horvath T, Lux M, Venturini L, Bar A, Kensah G, Lara AR, Tudorache I, Cebotari S, Hilfiker-Kleiner D, Haverich A, Hilfiker A. Generation of Bioartificial Heart Tissue by Combining a Three-Dimensional Gel-Based Cardiac Construct with Decellularized Small Intestinal Submucosa. Tissue Eng Part A. 2014;20(3-4):799-809.

Martens A, Rojas SV, Baraki H, Rathert C, Schecker N, Hernandez SR, Schwanke K, Zweigerdt R, Martin U, Saito S, Haverich A, Kutschka I. Macroscopic Fluorescence Imaging: A Novel Technique to Monitor Retention and Distribution of Injected Microspheres in an Experimental Model of Ischemic Heart Failure. PLoS One. 2014;9(8):e101775.

Martens A, Rojas SV, Baraki H, Rathert C, Schecker N, Zweigerdt R, Schwanke K, Rojas-Hernandez S, Martin U, Saito S, Schmitto JD, Haverich A, Kutschka I. Substantial Early Loss of Induced Pluripotent Stem Cells Following Transplantation in Myocardial Infarction. Artif Organs. 2014;38(11):978-84.

2013

Neumann A, Cebotari S, Tudorache I, Haverich A, Sarikouch S. Heart Valve Engineering: Decellularized Allograft Matrices in Clinical Practice. Biomed Tech (Berl). 2013;58(5):453-6.

Emmert MY, Emmert LS, Martens A, Ismail I, Schmidt-Richter I, Gawol A, Seifert B, Haverich A, Martin U, Gruh I. Higher Frequencies of Bcrp+ Cardiac Resident Cells in Ischaemic Human Myocardium. Eur Heart J. 2013;34(36):2830-8.

Schilling T, Brandes G, Tudorache I, Cebotari S, Hilfiker A, Meyer T, Biskup C, Bauer M, Waldmann KH, Bach FW, Haverich A, Hassel T. In Vivo Degradation of Magnesium Alloy La63 Scaffolds for Temporary Stabilization of Biological Myocardial Grafts in a Swine Model. Biomed Tech (Berl). 2013;58(5):407-16.

Tudorache I, Calistru A, Baraki H, Meyer T, Hoffler K, Sarikouch S, Bara C, Gorler A, Hartung D, Hilfiker A, Haverich A, Cebotari S. Orthotopic Replacement of Aortic Heart Valves with Tissue-Engineered Grafts. Tissue Eng Part A. 2013;19(15-16):1686-94.

2006 - 2012

2011

Mauritz C, Martens A, Rojas SV, Schnick T, Rathert C, Schecker N, Menke S, Glage S, Zweigerdt R, Haverich A, Martin U, Kutschka I. Induced Pluripotent Stem Cell (Ipsc)-Derived Flk-1 Progenitor Cells Engraft, Differentiate, and Improve Heart Function in a Mouse Model of Acute Myocardial Infarction. Eur Heart J. 2011;32(21):2634-41.

Cebotari S, Tudorache I, Ciubotaru A, Boethig D, Sarikouch S, Goerler A, Lichtenberg A, Cheptanaru E, Barnaciuc S, Cazacu A, Maliga O, Repin O, Maniuc L, Breymann T, Haverich A. Use of Fresh Decellularized Allografts for Pulmonary Valve Replacement May Reduce the Reoperation Rate in Children and Young Adults: Early Report. Circulation. 2011;124(11 Suppl):S115-23.

2009

Tudorache I, Kostin S, Meyer T, Teebken O, Bara C, Hilfiker A, Haverich A, Cebotari S. Viable Vascularized Autologous Patch for Transmural Myocardial Reconstruction. Eur J Cardiothorac Surg. 2009;36(2):306-11; discussion 11.

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