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| AATS/NHLBI: Cardiothoracic Surgery Exploring Collaborative Clinical Research Opportunities |
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Title and Author Prospects for Clinical Application of Tissue Engineered Cardiac ValvesJohn E. Mayer, M.D. Abstract Tissue engineering offers the prospect of in vitro fabrication of living cardiovascular tissue substitutes for implantation in order to overcome the shortcomings of current prosthetic and bioprosthetic materials, which include thrombogenicity, limited bioprosthetic leaflet durability, resistance to infection, and lack of growth potential. Outstanding questions in the development of tissue engineered valve tissue include the choice of cell type(s), the choice of scaffold materials to provide structural integrity and spatial organization for cells, techniques to modify scaffolds before or after cell seeding to direct cellular behavior, and ultimately, the ability of tissue engineered structures to function over the long term in the cardiovascular system. Early human experience with cell seeded tissue engineered pulmonary artery patches and intracardiac baffles demonstrated satisfactory function1, but there is only a very small reported valve tissue experience in man2. Experimental animal results with valve structures based on biodegradable scaffolds and bone marrow mesenchymal stem cells have demonstrated the ability to develop cardiac valves which have satisfactory initial function, but valve competence deteriorates over time3. Approaches based on cell seeding of previously decellularized valve matrix materials have also shown satisfactory short term function (Haverich reference), but the long term in vivo information is quite limited. In addition, decellularization processes may alter extracellular matrix and consequently alter cellular activity. Theoretically attractive, but unproven, alternative approaches include "smart" scaffolds which propose to selectively attract the "right" cells to populate the matrix after implantation. There are emerging opportunities for translation of current laboratory work into clinical trials. The major challenge for clinical application of cellularized valve replacement tissues is the development of improved in vitro fabrication techniques that translate into improved long term function in the cardiovascular system. These clinical applications will require establishment and use of facilities with �good manufacturing processes� and the further development of a regulatory process within the Food and Drug Administration. Candidate groups for initial clinical use of these tissue engineered valve structures should include use in the right side of the circulation, such as the pulmonary valve in patients with congenital defects such as tetralogy of Fallot and in the repair of the tricuspid valve, since these applications lack catastrophic hemodynamic consequences for valve failure. Human trials with decellularized homograft tissue that is seeded with autologous endothelial progenitor cells in the pulmonary valve position are underway in Europe. Key Research Gap Requiring NHLBI Leadership Improve long-term performance of tissue engineered constructs in-vivo. Key Citations 1: Shin�oka, T et al. Midterm clinical result of tissue-engineered vascular autografts seeded with autologous bone marrow cells. JTCVS 2005; 129(6):1330-8. 2: Cebotari S, et al. Clinical Application of Tissue Engineered Human Heart Valves Using Autologous Progenitor Cells. Circulation. 2006; 114: I132-I137. 3: Gottlieb D, et al. In vivo monitoring of function of autologous engineered pulmonary valve. J Thorac Cardiovasc Surg 2010; 139:723-31. |
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Copyright © 2012 American Association for Thoracic Surgery
All rights reserved. IMPORTANT REMINDER: The preceding information is intended only to provide
general guidance and not as a definitive basis for diagnosis or treatment in any particular case.
It is very important that you consult a doctor about any specific medical problem or question.
All rights reserved. IMPORTANT REMINDER: The preceding information is intended only to provide
general guidance and not as a definitive basis for diagnosis or treatment in any particular case.
It is very important that you consult a doctor about any specific medical problem or question.