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Re: Development of a next-generation tissue valve using a glutaraldehyde-fixed porcine aortic valve treated with decellularization, -galactosidase, space filler, organic solvent and detoxification

Re: Development of a next-generation tissue valve using a glutaraldehyde-fixed porcine aortic... 114 H.-G. Lim et al. / European Journal of Cardio-Thoracic Surgery European Journal of Cardio-Thoracic Surgery 48 (2015) 114 EDITORIAL COMMENT doi:10.1093/ejcts/ezu432 Advance Access publication 10 November 2014 Cite this article as: Parolari A, Songia P, Myasoedova V, Poggio P. Re: Development of a next-generation tissue valve using a glutaraldehyde-fixed porcine aortic valve treated with decellularization, α-galactosidase, space filler, organic solvent and detoxification. Eur J Cardiothorac Surg 2015;48:114. Re: Development of a next-generation tissue valve using a glutaraldehyde-fixed porcine aortic valve treated with decellularization, α-galactosidase, space filler, organic solvent and detoxification a, b a b Alessandro Parolari *, Paola Songia , Veronika Myasoedova and Paolo Poggio Unit for Clinical Research in Atherothrombosis, Centro Cardiologico Monzino IRCCS, Milan, Italy Unit for the Study of Aortic, Valvular and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Milan, Italy * Corresponding author. Dipartimento di Scienze Cardiovascolari, Università degli Studi di Milano, Centro Cardiologico Monzino IRCCS, Via Parea 4, 20138 Milan, Italy. Tel: +39-2-580021; fax: +39-2-580002750; e-mail: alessandro.parolari@cardiologicomonzino.it (A. Parolari). Keywords: Aortic valve development � Xenograft � Galactose-alpha-1,3-galactose � Valve durability Bioprosthetic heart valves are made with porcine aortic valves or procedure could be very useful to produce new long-lasting heart constructed with bovine pericardium, both cross-linked with glu- valves, maybe even usable in younger patients. taraldehyde (GA). The main problem with bioprosthetic valves is Finally, an intriguing challenge will be to identify biomarkers tissue degeneration owing to tissue fatigue and calcification [1]. able to follow and predict valve durability, as well as to identify The GA fixation is commonly used to provide resistance to bio- very early signs of valve failure. Now, we know that biomarkers, degradability and to reduce the antigenic host response. Unfortu- depending on their capacity to change over time, can be easily nately, the major cause of GA-fixed valve failure is dystrophic classified into: (i) static markers, which do not change over time calcification. This degeneration occurs due to the aldehyde groups’ and are almost synonymous with genetic markers and (ii) dynamic phospholipids and immunological response [2]. markers, which change over time. Both static and dynamic Particularly, GA fixation does not guarantee complete tissue bio- markers can be useful in the identification of valve degeneration. compatibility because it leaves Galactose-alpha-1,3-galactose (aGal) Dynamic biomarkers could monitor the status of the valves with a epitopes untouched [2]. Furthermore, implantation of bioprosthetic simple blood test performed periodically, whereas static markers valves significantly increases the circulating anti-aGal immuno- could be used to identify patients susceptible to fast prosthesis globulin M and immunoglobulin G already after 10 days of the im- degradation. In the near future, we expect to see interesting plantation and these increases seem to persist over time [2–4]. The results coming from the collaboration of researchers and clinicians inactivation of such an epitope should be mandatory to meet the in this very important translational approach to bioprosthetic requirements for safe clinical application [2]. valve degeneration. Lim et al. propose the development of a new GA-fixed porcine aortic valve treated in five steps, where they combine multiple anticalcification strategies to potentially solve xenograft biocom- REFERENCES patibility [5]. The complete decellularization combined with the alpha-galactosidase treatment completely inactivates aGal epi- [1] David TE. Surgical treatment of aortic valve disease. Nat Rev Cardiol 2013; 10:375–86. topes and makes the resulting xenograft a great candidate to [2] Naso F, Gandaglia A, Bottio T, Tarzia V, Nottle MB, d’Apice AJ et al. First reduce or even eliminate the antigenic host response. In addition, quantification of alpha-Gal epitope in current glutaraldehyde-fixed heart they extracted phospholipids with an ethanol/octanol solution to valve bioprostheses. Xenotransplantation 2013;20:252–61. reduce the calcification potential of the aldehyde groups. Further- [3] Konakci KZ, Bohle B, Blumer R, Hoetzenecker W, Roth G, Moser B et al. more, they proved the feasibility of the procedure by first using a Alpha-Gal on bioprostheses: xenograft immune response in cardiac surgery. Eur J Clin Invest 2005;35:17–23. mock circulation and then implanting the treated valves in sheep. [4] Mangold A, Szerafin T, Hoetzenecker K, Hacker S, Lichtenauer M, The only concern is the sheep model, because it is questionable Niederpold T et al. Alpha-Gal specific IgG immune response after implant- if an animal that carries the aGal gene is capable of producing a ation of bioprostheses. Thorac Cardiovasc Surg 2009;57:191–5. high anti-aGal titre. In our opinion, however, it would be neces- [5] Lim H-G, Kim GB, Jeong S, Kim YJ. Development of a next-generation tissue valve using a glutaraldehyde-fixed porcine aortic valve treated with decel- sary to evaluate the implantation of these new xenografts in a lularization, α-galactosidase, space filler, organic solvent and detoxification. species that already express anti-aGal such as Old World primates. Eur J Cardiothorac Surg 2015;48:104–13. Currently, no xenograft treatment is able to completely mask or [6] McGregor CG, Kogelberg H, Vlasin M, Byrne GW. Gal-knockout bioprosth- inactivate aGal epitopes. Only valves derived from aGal knockout eses exhibit less immune stimulation compared to standard biological pigs have been studied with interesting results [6], but this new heart valves. J Heart Valve Dis 2013;22:383–90. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

Re: Development of a next-generation tissue valve using a glutaraldehyde-fixed porcine aortic valve treated with decellularization, -galactosidase, space filler, organic solvent and detoxification

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Publisher
Oxford University Press
Copyright
The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
ISSN
1010-7940
eISSN
1873-734X
DOI
10.1093/ejcts/ezu432
pmid
25385220
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Abstract

114 H.-G. Lim et al. / European Journal of Cardio-Thoracic Surgery European Journal of Cardio-Thoracic Surgery 48 (2015) 114 EDITORIAL COMMENT doi:10.1093/ejcts/ezu432 Advance Access publication 10 November 2014 Cite this article as: Parolari A, Songia P, Myasoedova V, Poggio P. Re: Development of a next-generation tissue valve using a glutaraldehyde-fixed porcine aortic valve treated with decellularization, α-galactosidase, space filler, organic solvent and detoxification. Eur J Cardiothorac Surg 2015;48:114. Re: Development of a next-generation tissue valve using a glutaraldehyde-fixed porcine aortic valve treated with decellularization, α-galactosidase, space filler, organic solvent and detoxification a, b a b Alessandro Parolari *, Paola Songia , Veronika Myasoedova and Paolo Poggio Unit for Clinical Research in Atherothrombosis, Centro Cardiologico Monzino IRCCS, Milan, Italy Unit for the Study of Aortic, Valvular and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Milan, Italy * Corresponding author. Dipartimento di Scienze Cardiovascolari, Università degli Studi di Milano, Centro Cardiologico Monzino IRCCS, Via Parea 4, 20138 Milan, Italy. Tel: +39-2-580021; fax: +39-2-580002750; e-mail: alessandro.parolari@cardiologicomonzino.it (A. Parolari). Keywords: Aortic valve development � Xenograft � Galactose-alpha-1,3-galactose � Valve durability Bioprosthetic heart valves are made with porcine aortic valves or procedure could be very useful to produce new long-lasting heart constructed with bovine pericardium, both cross-linked with glu- valves, maybe even usable in younger patients. taraldehyde (GA). The main problem with bioprosthetic valves is Finally, an intriguing challenge will be to identify biomarkers tissue degeneration owing to tissue fatigue and calcification [1]. able to follow and predict valve durability, as well as to identify The GA fixation is commonly used to provide resistance to bio- very early signs of valve failure. Now, we know that biomarkers, degradability and to reduce the antigenic host response. Unfortu- depending on their capacity to change over time, can be easily nately, the major cause of GA-fixed valve failure is dystrophic classified into: (i) static markers, which do not change over time calcification. This degeneration occurs due to the aldehyde groups’ and are almost synonymous with genetic markers and (ii) dynamic phospholipids and immunological response [2]. markers, which change over time. Both static and dynamic Particularly, GA fixation does not guarantee complete tissue bio- markers can be useful in the identification of valve degeneration. compatibility because it leaves Galactose-alpha-1,3-galactose (aGal) Dynamic biomarkers could monitor the status of the valves with a epitopes untouched [2]. Furthermore, implantation of bioprosthetic simple blood test performed periodically, whereas static markers valves significantly increases the circulating anti-aGal immuno- could be used to identify patients susceptible to fast prosthesis globulin M and immunoglobulin G already after 10 days of the im- degradation. In the near future, we expect to see interesting plantation and these increases seem to persist over time [2–4]. The results coming from the collaboration of researchers and clinicians inactivation of such an epitope should be mandatory to meet the in this very important translational approach to bioprosthetic requirements for safe clinical application [2]. valve degeneration. Lim et al. propose the development of a new GA-fixed porcine aortic valve treated in five steps, where they combine multiple anticalcification strategies to potentially solve xenograft biocom- REFERENCES patibility [5]. The complete decellularization combined with the alpha-galactosidase treatment completely inactivates aGal epi- [1] David TE. Surgical treatment of aortic valve disease. Nat Rev Cardiol 2013; 10:375–86. topes and makes the resulting xenograft a great candidate to [2] Naso F, Gandaglia A, Bottio T, Tarzia V, Nottle MB, d’Apice AJ et al. First reduce or even eliminate the antigenic host response. In addition, quantification of alpha-Gal epitope in current glutaraldehyde-fixed heart they extracted phospholipids with an ethanol/octanol solution to valve bioprostheses. Xenotransplantation 2013;20:252–61. reduce the calcification potential of the aldehyde groups. Further- [3] Konakci KZ, Bohle B, Blumer R, Hoetzenecker W, Roth G, Moser B et al. more, they proved the feasibility of the procedure by first using a Alpha-Gal on bioprostheses: xenograft immune response in cardiac surgery. Eur J Clin Invest 2005;35:17–23. mock circulation and then implanting the treated valves in sheep. [4] Mangold A, Szerafin T, Hoetzenecker K, Hacker S, Lichtenauer M, The only concern is the sheep model, because it is questionable Niederpold T et al. Alpha-Gal specific IgG immune response after implant- if an animal that carries the aGal gene is capable of producing a ation of bioprostheses. Thorac Cardiovasc Surg 2009;57:191–5. high anti-aGal titre. In our opinion, however, it would be neces- [5] Lim H-G, Kim GB, Jeong S, Kim YJ. Development of a next-generation tissue valve using a glutaraldehyde-fixed porcine aortic valve treated with decel- sary to evaluate the implantation of these new xenografts in a lularization, α-galactosidase, space filler, organic solvent and detoxification. species that already express anti-aGal such as Old World primates. Eur J Cardiothorac Surg 2015;48:104–13. Currently, no xenograft treatment is able to completely mask or [6] McGregor CG, Kogelberg H, Vlasin M, Byrne GW. Gal-knockout bioprosth- inactivate aGal epitopes. Only valves derived from aGal knockout eses exhibit less immune stimulation compared to standard biological pigs have been studied with interesting results [6], but this new heart valves. J Heart Valve Dis 2013;22:383–90.

Journal

European Journal of Cardio-Thoracic Surgery – Oxford University Press

Published: Jul 10, 2015

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