Searching for the optimal heart valve

Stock, Ulrich A.

doi:10.1002/biot.201200341

Cited by 5 publications

(1 citation statement)

References 10 publications

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“…Regarding their limitation, non‐immunogeneic decellularized porcine heart valves (dpHV) would be a close and suitable alternative. Similar to decellularized human allografts, dpHV are intended as scaffolds for in situ tissue engineering, being physiologically fully assimilated by the recipient minimizing the incidence of follow‐up replacement surgeries 10. This would be a clear advantage over traditional bioprosthetic, glutaraldehyde cross‐linked pig heart valves that are available as medical devices for more than 40 years 5.…”

Section: Introductionmentioning

confidence: 99%

Decellularized pig pulmonary heart valves—Depletion of nucleic acids measured by proviral PERV pol

Godehardt

Ramm

Gulich

et al. 2019

Xenotransplantation

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Background: Decellularized human pulmonary heart valve (dhHV) scaffolds have been shown to be the gold standard especially for younger, adolescent patients.However, human heart valves are limited in availability. Xenogeneic decellularized pig heart valves (dpHV) may serve as alternative. Methods:The efficacy of DNA reduction processes upon decellularization of heart valves from German Landrace pigs was analyzed by measurements of remaining nucleic acids including proviral porcine endogenous retrovirus (PERV) sequences.Porcine pulmonary heart valves (pPHV) were decellularized by three different protocols and further treated with DNaseI or Benzonase, at varying incubation times.DNA isolated from valve associated muscle (m), valve cusp (c), and pulmonary artery (pa) was monitored by PCR and qRT-PCR using GAPDH and the PERV polymerase (pol) for read-out.Results: Decellularization of pPHV led to a significant reduction of DNA (>99%) which could be further significantly increased for (m) and (pa) by nuclease treatment, reducing proviral PERV pol from approximately 5 × 10 7 to 5 × 10 3 copies/mg in nuclease treated tissues. Conclusions:Both nucleases demonstrated comparable activities. But DNaseI revealed to be less consistent for PERV, especially at muscular tissue. Noteworthy, remaining proviral sequences are still detectable by PCR; however, due to the absence of the cellular replication machinery the production of infectious particles is not expected. Decellularization and nuclease treatment of pPHV is an efficient procedure to reduce the DNA content including PERV, thus represents a valuable option to increase virus safety independently from the source animal background. K E Y W O R D SPERV, virus safety, xenogeneic decellularized heart valve

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Section: Introductionmentioning

confidence: 99%

Decellularized pig pulmonary heart valves—Depletion of nucleic acids measured by proviral PERV pol

Godehardt

Ramm

Gulich

et al. 2019

Xenotransplantation

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Editorial: Strategies in tissue engineering and regenerative medicine

Schenke‐Layland

Walles²

2013

Biotechnology Journal

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"Strategies in Tissue Engineering": this special issue is edited by Prof. Katja Schenke-Layland and Prof. Heike Walles and covers many salient aspects of tissue engineering and regenerative medicine. The issue includes articles on Raman spectroscopy and its application in tissue engineering; bioreactor design and surface functionalization for tissue culture applications; improved method for RNA isolation from tissue samples and much more.

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Decellularized GGTA1-KO pig heart valves do not bind preformed human xenoantibodies

et al. 2016

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Pre-clinical and clinical data have unequivocally demonstrated the usefulness of decellularized heart valve (HV) matrices implanted for HV replacement therapy. However, human donor valves applicable for decellularization are in short supply, which prompts the search for suitable alternatives, such as porcine grafts. Since decellularization might be insufficient to remove all xenoantigens, we analysed the interaction of human preformed antibodies with decellularized porcine HV in vitro to assess potential immune reactions upon implantation. Detergent-decellularized pulmonary HV from German Landrace wild-type (wt) or α1,3-galactosyltransferase knockout (GGTA1-KO) pigs were investigated by inhibition ELISA and GSL I-B4 staining to localize and quantify matrix-bound αGal epitopes, which represent the most prominent xenoantigen. Additionally, preformed human xenoantibodies were affinity purified by perfusing porcine kidneys. Binding of purified human antibodies to decellularized HV was investigated by inhibition ELISA. Furthermore, binding of human plasma proteins to decellularized matrices was determined by western blot. Decellularized human pulmonary artery served as controls. Decellularization of wt HV led to a reduction of αGal epitopes by 70 %. Residual epitopes were associated with the subendothelial extracellular matrix. As expected, no αGal epitopes were found on decellularized GGTA1-KO matrix. The strongest binding of preformed human anti-pig antibodies was found on wt matrices, whereas GGTA1-KO matrices bound similar or even fewer xenoantibodies than human controls. These results demonstrate the suitability of GGTA1-KO pigs as donors for decellularized heart valves for human patients. Besides the presence of αGal antibodies on decellularized heart valves, no further preformed xenoantibodies against porcine matrix were detected in tested human sera.

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Searching for the optimal heart valve

Cited by 5 publications

References 10 publications

Decellularized pig pulmonary heart valves—Depletion of nucleic acids measured by proviral PERV pol

Decellularized pig pulmonary heart valves—Depletion of nucleic acids measured by proviral PERV pol

Editorial: Strategies in tissue engineering and regenerative medicine

Decellularized GGTA1-KO pig heart valves do not bind preformed human xenoantibodies

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