Skip to main content
SpringerLink
Log in

Tissue-Engineering von Atrioventrikularklappen

Tissue engineering of atrioventricular valves

  • Stand der Wissenschaft
  • Published:
Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Einleitung

Das Tissue-Engineering von Herzklappen ermöglicht die potenzielle Herstellung von autologen Gewebekonstrukten, um Limitationen des chirurgischen Herzklappenersatzes wie z. B. Gewebekompatibilität und Langzeitfunktion zu optimieren.

Methoden und Ergebnisse

Mitral- und Trikuspidalklappen von Schweinen der Deutschen Landrasse wurden im Rahmen des routinemäßigen Schlachtprozesses gewonnen und einem standardisierten Dezellularisierungsprozess unterzogen. Daran schloss sich die Rezellularisierung mit in vitro expandierten humanen Nabelschnurendothelzellen an. Die mikroskopische und die spektrofotometrische Analyse zeigten nach Dezellularisierung eine erhaltene extrazelluläre Matrix sowie Biomechanik der Klappengerüste. Darüber hinaus konnten die humanen Endothelzellen erfolgreich, unter Zuhilfenahme eines Bioreaktors, auf der Oberfläche der zellfreien Herzklappensegel unter physiologischen Bedingungen angesiedelt werden und eine geschlossene Zelldecke bilden.

Schlussfolgerung

Anhand unserer Versuche konnten wir erstmals die Möglichkeit aufzeigen, xenogene Atrioventrikularklappen mit potenziell autologen humanen Nabelschnurzellen unter physiologischen Bedingungen im Bioreaktor zu besiedeln.

Abstract

Introduction

Tissue engineering enables the potential fabrication of autologous heart valve neoscaffolds to improve limitations of surgical heart valve therapy, such as tissue compatibility and long-term function.

Methods and results

Mitral and tricuspid valves were harvested from the hearts of German Landrace swine during routine slaughtering at an abattoir and decellularized under standardized conditions. Recellularization was carried out with in vitro expanded human umbilical cord-derived endothelial cells (HUDEC), which were seeded onto the heart valve neoscaffolds. Microscopic and quantitative analysis demonstrated a maintained extracellular matrix as well as mechanical stability of the heart valve neoscaffolds after decellularization. The surface of the xenogeneic matrix could be successfully reseeded with a confluent layer of in vitro expanded HUDEC under physiological flow conditions in a bioreactor.

Conclusion

These results facilitate future research towards the fabrication of autologous atrioventricular heart valve neoscaffolds on the basis of decellularized xenogeneic tissue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6
Abb. 7

Literatur

  1. Roger VL, Go AS (2012) Executive Summary: heart disease and stroke statistics – 2012 update: a report from the American Heart Association. Circulation 125(1):188–197

    Article  PubMed  Google Scholar 

  2. Ptaszek LM, Mansour M, Ruskin JN, Chien KR (2012) Towards regenerative therapy for cardiac disease. Lancet 379(9819):933–942

    Article  PubMed  Google Scholar 

  3. Teebken OE, Puschmann C, Rohde B, Burgwitz K, Winkler M, Pichlmaier AM, Weidemann J, Haverich A (2009) Human iliac vein replacement with a tissue-engineered graft. Vasa 38(1):60–65 (Feb) doi:10.1024/0301-1526.38.1.60

    Article  CAS  PubMed  Google Scholar 

  4. Dohmen PM, Lembcke A, Holinski S, Pruss A, Konertz W (2011) Ten years of clinical results with a tissue-engineered pulmonary valve. Ann Thorac Surg 92(4):1308–1314. doi:10.1016/j.athoracsur.2011.06.009.

    Article  PubMed  Google Scholar 

  5. Cebotari S, Lichtenberg A, Tudorache I, Hilfiker A, Mertsching H, Leyh R, Breymann T, Kallenbach K, Maniuc L, Batrinac A, Repin O, Maliga O, Ciubotaru A, Haverich A (2006) Clinical application of tissue engineered human heart valves using autologous progenitor cells. Circulation 114(1 Suppl):I132–7 (Jul)

    PubMed  Google Scholar 

  6. Neethling WM, Strange G, Firth L, Smit FE (2013) Evaluation of a tissue-engineered bovine pericardial patch in paediatric patients with congenital cardiac anomalies: initial experience with the ADAPT-treated CardioCel(R) patch. Interact Cardiovasc Thorac Surg 17(4):698–702. doi:10.1093/icvts/ivt268.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, Taylor DA (2008) Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med 14(2):213–221. doi:10.1038/nm1684.

    Article  CAS  PubMed  Google Scholar 

  8. Mayer JE Jr. (1995) Uses of homograft conduits for right ventricle to pul- monary artery connections in the neonatal period. Semin Thorac Car- Diovasc Surg 7:130–132

    Google Scholar 

  9. Schoen FJ, Levy RJ (1999) Founder’s award, 25th Annual Meeting of the Society for Biomaterials, perspectives. Providence, rhode island, april 28–may 2, 1999. Tissue heart valves: current challenges and future research perspectives. J Biomed Mater Res 47:439–465

    Article  CAS  PubMed  Google Scholar 

  10. Turrentine MW, Ruzmetov M, Vijay P, Bills RG, Brown JW (2001) Biological versus mechanical aortic valve replacement in children. Ann Thorac Surg 71(5):356–360

    Article  Google Scholar 

  11. Homann M, Haehnel JC, Mendler N, Paek SU, Holper K, Meisner H, Lange R (2000) Reconstruction of the RVOT with valved biological conduits: 25 years experience with allografts and xenografts. Eur J Cardiothorac Surg 17:624–630

    Article  CAS  PubMed  Google Scholar 

  12. Yacoub M, Rasmi NR, Sundt TM, Lund O, Boyland E, Radley-Smith R, Khaghani A, Mitchell A (1995) Fourteen-year experience with homovital homografts for aortic valve replacement. J Thorac Cardiovasc Surg 110:186–193

    Article  CAS  PubMed  Google Scholar 

  13. da Costa FD, Dohmen PM, Duarte D, von Glenn C, Lopes SV, Filho HH, da Costa MB, Konertz W (2005) Immunological and echocardiographic evaluation of decellularized versus cryopreserved allografts during the Ross operation. Eur J Cardiothorac Surg 27:572–578

    Article  PubMed  Google Scholar 

  14. Vacanti JP, Langer R (1999) Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet 354(Suppl 1):S132–S134

    Google Scholar 

  15. Bell E, Ivarsson B, Merrill C (1979) Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci Usa 76(3):1274–1278

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Langer R, Vacanti JP (1993) Tissue Eng. Science 260(5110):920–926

    Article  CAS  PubMed  Google Scholar 

  17. Barratt-Boyes BG (1965) A method for preparing and inserting a homograft aortic valve. Br J Surg 52(11):847–856 (Nov)

    Article  CAS  PubMed  Google Scholar 

  18. Ross D (1967) Homograft replacement of the aortic valve. Br J Surg 54(10):842–843

    Article  CAS  PubMed  Google Scholar 

  19. O’Brien MF, Goldstein S, Walsh S, Black KS, Elkins R, Clarke D (1999) The SynerGraft valve: a new acellular (nonglutaraldehyde-fixed) tissue heart valve for autologous recellularization first experimental studies before clinical implantation. Semin Thorac Cardiovasc Surg 11(4 Suppl 1):194–200

    PubMed  Google Scholar 

  20. Wilhelmi MH, Mertsching H, Wilhelmi M, Leyh R, Haverich A (2003) Role of inflammation in allogeneic and xenogeneic heart valve degeneration: immunohistochemical evaluation of inflammatory endothelial cell activation. J Heart Valve Dis 12(4):520–526 (Jul)

    PubMed  Google Scholar 

  21. Wilhelmi MH, Rebe P, Leyh R, Wilhelmi M, Haverich A, Mertsching H (2003) Role of inflammation and ischemia after implantation of xenogeneic pulmonary valve conduits: histological evaluation after 6 to 12 months in sheep. Int J Artif Organs 26(5):411–420 (May)

    CAS  PubMed  Google Scholar 

  22. Gulbins H, Goldemund A, Uhlig A, Pritisanac A, Meiser B, Reichart B (2003) Implantation of an autologously endothelialized homograft. J Thorac Cardiovasc Surg 126(3):890–891 (Sep)

    Article  PubMed  Google Scholar 

  23. Dohmen PM, Lembcke A, Holinski S, Kivelitz D, Braun JP, Pruss A, Konertz W (2007) Mid-term clinical results using a tissue-engineered pulmonary valve to reconstruct the right ventricular outflow tract during the Ross procedure. Ann Thorac Surg 84(3):729–736 (Sep)

    Article  PubMed  Google Scholar 

  24. Konertz W, Angeli E, Tarusinov G, Christ T, Kroll J, Dohmen PM, Krogmann O, Franzbach B, Pace Napoleone C, Gargiulo G (2011) Right ventricular outflow tract reconstruction with decellularized porcine xenografts in patients with congenital heart disease. J Heart Valve Dis 20(3):341–347 (May)

    PubMed  Google Scholar 

  25. Driessen-Mol A, Emmert MY, Dijkman PE, Frese L, Sanders B, Weber B, Cesarovic N, Sidler M, Leenders J, Jenni R, Grünenfelder J, Falk V, Baaijens FP, Hoerstrup SP (2014) Transcatheter implantation of homologous „off-the-shelf“ tissue-engineered heart valves with self-repair capacity: long-term functionality and rapid in vivo remodeling in sheep. J Am Coll Cardiol 63(13):1320–1329. doi:10.1016/j.jacc.2013.09.082.

    Article  PubMed  Google Scholar 

  26. Schmidt D, Dijkman PE, Driessen-Mol A, Stenger R, Mariani C, Puolakka A, Rissanen M, Deichmann T, Odermatt B, Weber B, Emmert MY, Zund G, Baaijens FP, Hoerstrup SP (2010) Minimally-invasive implantation of living tissue engineered heart valves: a comprehensive approach from autologous vascular cells to stem cells. J Am Coll Cardiol 56(6):510–520. doi:10.1016/j.jacc.2010.04.024.

    Article  PubMed  Google Scholar 

  27. Metzner A, Stock UA, Iino K, Fischer G, Huemme T, Boldt J, Braesen JH, Bein B, Renner J, Cremer J, Lutter G (2010) Percutaneous pulmonary valve replacement: autologous tissue-engineered valved stents. Cardiovasc Res 88(3):453–461. doi:10.1093/cvr/cvq212.

    Article  CAS  PubMed  Google Scholar 

  28. Lauten A, Laube A, Schubert H, Bischoff S, Nietzsche S, Horstkötter K, Poudel-Bochmann B, Franz M, Lichtenberg A, Figulla HR, Akhyari P (2014) Transcatheter treatment of tricuspid regurgitation by caval valve implantation-experimental evaluation of decellularized tissue valves in central venous position. Catheter Cardiovasc Interv 85(1):150–160

    Article  PubMed  Google Scholar 

  29. Shinoka T, Breuer CK, Tanel RE, Zund G, Miura T, Ma PX, Langer R, Vacanti JP, Mayer JE Jr. (1995) Tissue engineering heart valves: valve leaflet replacement study in a lamb model. Ann Thorac Surg 60(6):513–516

    Article  Google Scholar 

  30. Shinoka T, Shum-Tim D, Ma PX, Tanel RE, Isogai N, Langer R, Vacanti JP, Mayer JE Jr. (1998) Creation of viable pulmonary artery autografts through tissue engineering. J Thorac Cardiovasc Surg 115:536–546

    Article  CAS  PubMed  Google Scholar 

  31. Lutolf MP, Hubbell JA (2005) Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 23:47–55

    Article  CAS  PubMed  Google Scholar 

  32. Stock UA, Nagashima M, Khalil PN, Nollert GD, Herden T, Sperling JS, Moran A, Lien J, Martin DP, Schoen FJ, Vacanti JP, Mayer JE Jr. (2000) Tissue-engineered valved conduits in the pulmonary circulation. J Thorac Cardiovasc Surg 19(4 Pt 1):732–740

    Article  Google Scholar 

  33. Hoerstrup SP, Sodian R, Daebritz S, Wang J, Bacha EA, Martin DP, Moran AM, Guleserian KJ, Sperling JS, Kaushal S, Vacanti JP, Schoen FJ, Mayer JE Jr. (2000) Functional living trileaflet heart valves grown in vitro. Circulation 102(19 Suppl 3):III44–III49 (Nov)

    CAS  PubMed  Google Scholar 

  34. Weymann A, Schmack B, Okada T, Soos P, Istok R, Radovits T, Straub B, Barnucz E, Loganathan S, Paetzold I, Chaimow N, Schies C, Korkmaz S, Tochtermann U, Karck M, Szabo G (2012) Reendothelialization of human heart valve neoscaffolds using umbilical cord derived endothelial cells. Circ J 77(1):207–216

    Article  PubMed  Google Scholar 

  35. Hodde JP, Record RD, Tullius RS, Badylak SF (2002) Retention of endothelial cell adherence to porcine-derived extracellular matrix after disinfection and sterilization. Tissue Eng 8:225–234

    Article  CAS  PubMed  Google Scholar 

  36. Pankajakshan D, Krishnan LK (2009) Design of fibrin matrix composition to enhance endothelial cell growth and extracellular matrix deposition for in vitro tissue engineering. Artif Organs 33:16–25

    Article  CAS  PubMed  Google Scholar 

  37. Kasimir MT, Rieder E, Seebacher G, Silberhumer G, Wolner E, Weigel G, Simon P (2003) Comparison of different decellularization procedures of porcine heart valves. Int J Artif Organs 26:421–427

    CAS  PubMed  Google Scholar 

  38. Grauss RW, Hazekamp MG, van Vliet S, Gittenberger- de Groot AC, DeRuiter MC (2003) Decellularization of rat aortic valve allografts reduces leaflet destruction and extracellular matrix remodeling. J Thorac Cardiovasc Surg 126:2003–2010

    Article  CAS  PubMed  Google Scholar 

  39. Lichtenberg A, Cebotari S, Tudorache I, Sturz G, Winterhalter M, Hilfiker A, Haverich A (2006) Flow-dependent re-endothelialization of tissue-engineered heart valves. J Heart Valve Dis 15:287–293

    PubMed  Google Scholar 

  40. Leask RL, Jain N, Butany J (2003) Endothelium and valvular diseases of the heart. Microsc Res Tech 60:129–137

    Article  PubMed  Google Scholar 

  41. Keller BB (2007) New insights into the developmental biomechanics of the atrioventricular valves. Circ Res 100:1399–1401

    Article  CAS  PubMed  Google Scholar 

  42. Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103:1669–1675

    Article  CAS  PubMed  Google Scholar 

  43. Lu LL, Liu YJ, Yang SG, Zhao QJ, Wang X, Gong W, Han ZB, Xu ZS, Lu YX, Liu D, Chen ZZ, Han ZC (2006) Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica 91:1017–1026

    CAS  PubMed  Google Scholar 

  44. Stubbendorff M, Deuse T, Hua X, Phan TT, Bieback K, Atkinson K, Eiermann TH, Velden J, Schröder C, Reichenspurner H, Robbins RC, Volk HD, Schrepfer S (2013) Immunological properties of extraembryonic human mesenchymal stromal cells derived from gestational tissue. Stem Cells Dev 22:2619–2629

    Article  CAS  PubMed  Google Scholar 

  45. Reichardt A, Polchow B, Shakibaei M, Henrich W, Hetzer R, Lueders C (2013) Large scale expansion of human umbilical cord cells in a rotating bed system bioreactor for cardiovascular tissue engineering applications. Open Biomed Eng J 7:50–61

    Article  PubMed Central  PubMed  Google Scholar 

  46. Barron V, Lyons E, Stenson-Cox C, McHugh PE, Pandit A (2003) Bioreactors for cardiovascular cell and tissue growth: a review. Ann Biomed Eng 31:1017–1030

    Article  CAS  PubMed  Google Scholar 

  47. Blackman BR, Garcia-Cardena G, Gimbrone MA Jr. (2002) A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms. J Biomech Eng 124:397–407

    Article  PubMed  Google Scholar 

  48. Imberti B, Seliktar D, Nerem RM, Remuzzi A (2002) The response of endothelial cells to fluid shear stress using a co-culture model of the arterial wall. Endothelium 9:11–23

    Article  CAS  PubMed  Google Scholar 

  49. Jin ZG, Ueba H, Tanimoto T, Lungu AO, Frame MD, Berk BC (2003) Ligand-independent activation of vascular endothelial growth factor receptor 2 by fluid shear stress regulates activation of endothelial nitric oxide synthase. Circ Res 93:354–363

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Herzchirurgie, Herz und Marfan Zentrum, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland

    B. Schmack, G. Szabó, M. Karck &  A. Weymann

Authors
  1. B. Schmack
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Szabó
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Karck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Weymann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Weymann.

Ethics declarations

Interessenkonflikt

B. Schmack, G. Szambó, M. Karck und A. Weymann geben an, dass kein Interessenkonflikt besteht.

Alle nationalen Richtlinien zur Haltung und zum Umgang mit Labortieren wurden eingehalten und die notwendigen Zustimmungen der zuständigen Behörden liegen vor.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schmack, B., Szabó, G., Karck, M. et al. Tissue-Engineering von Atrioventrikularklappen. Z Herz- Thorax- Gefäßchir 29, 402–409 (2015). https://doi.org/10.1007/s00398-015-0028-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00398-015-0028-3

Schlüsselwörter

Keywords

Search

Navigation