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Ann Thorac Surg 2002;74:1434
© 2002 The Society of Thoracic Surgeons
a Section of Thoracic Surgery, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
* Address reprint requests to Dr Elkins, Section of Thoracic Surgery, University of Oklahoma Health Science Center, 920 Stanton L. Young Blvd, Suite WP2230, Oklahoma City, OK, 73190, USA.
e-mail: ronald-elkins{at}ouhsc.edu
| Dr Elkins discloses that he has a conflict of interest with CryoLife, Inc.
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The development of a tissue-engineered heart valve has been the goal of many cardiac surgeons for decades. The original implants of allograft heart valves were hoped to be permanent valve implants, especially if they could be implanted with viable intrinsic cells. However, these valves slowly develop progressive structural degeneration and at explantation are noted to be acellular. This loss of cellularity is thought to be immunologically mediated, as valvular tissue of organ transplants retain their normal cellular architecture if appropriate immune suppressive therapy is utilized. This recognition that maintenance of viability was important for long-term durability led to the use of the pulmonary autograft valve as a replacement for the aortic and mitral valve. The long-term function of the pulmonary valve in the systemic circulation and the requirement of a biological substitute for the pulmonary valve that converts single valve disease to two valves at risk of degeneration and failure are major deterrents to acceptance of the pulmonary autograft as the ideal aortic valve replacement.
Continued interest in development of a tissue-engineered valve has been focused in three different arenas: (1) Seeding a biodegradable valve matrix with autologous endothelial or fibroblast cells [1]; (2) seeding a decellularized allograft valve with vascular endothelial cells or dermal fibroblasts [2–4]; and (3) use of a decellularized allograft with maintained structural integrity as a valve implant that will be repopulated by adaptive remodeling [5–7].
Dohmen and coauthors[8] report their experience with their first successful implant of a decellularized allograft seeded with autologous vascular endothelial cells with 1-year follow-up. They are to be congratulated on this success, but there are also several questions still to be answered. Does their decellularization process render all allograft valves immunologically inert? Will the seeded vascular endothelial cells penetrate the matrix and differentiate into fibroblasts and myo-fibroblasts that are biologically active, and will they regenerate the collagen and elastin matrix of the allograft such that the valve will maintain structural integrity? Can their decellularization process be utilized on other cardiac valves such as the aortic valve, which has significant structural differences, especially the aortic root and ascending aorta?
Decellularized allografts are now being utilized as pulmonary and aortic valve replacements with anticipated repopulation of the leaflet tissue and of the conduit. Early assessment of valve function has been excellent, with evidence of reendothelialization and repopulation of the matrix with fibroblasts and myo-fibroblasts in a limited number of explants. In some patients, a humoral antibody response similar to the humoral immune response seen in most patients who receive a cryopreserved allograft has been demonstrated. It is anticipated that repopulation of the decellularized allograft will be associated with improved long-term function; however, this is still unknown. This is an exciting development in tissue valve engineering, but even if it would ultimately demonstrate that an allograft valve can be a permanent valve without late degeneration, its use is still limited by the availability of allograft valves.
The adaptation of these processes to xenograft tissue or the development of a biodegradable matrix that is seeded with autogenous endothelial or fibroblasts cells is the present hope for an unlimited supply of tissue-engineered heart valves. In vitro studies have been conducted and limited in vivo implants have been accomplished utilizing these techniques. Early results are promising, and we await further elucidation of these ongoing investigations in the hope of having a tissue-engineered valve that will meet the need for clinical heart valve replacement.
References
This article has been cited by other articles:
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  I. Vesely Heart Valve Tissue Engineering Circ. Res., October 14, 2005; 97(8): 743 - 755. [Abstract] [Full Text] [PDF]
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 P. G. Hogan and M. F. O'Brien Improving the allograft valve: does the immune response matter? J. Thorac. Cardiovasc. Surg., November 1, 2003; 126(5): 1251 - 1253. [Full Text] [PDF]
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