Skip to main content
SpringerLink
Log in

Transplantation of a decellularized mitral valve complex in pigs

  • Original Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Purpose

Conventional mitral valve replacement is associated with the loss of natural continuity of the mitral valve complex. This study evaluated the morphologic/histological characteristics and function of a decellularized mitral valve used as a transplantable graft.

Methods

Hearts excised from pigs were decellularized by perfusion using detergent. Grafts with the mitral annulus, valve, chordae, and papillary muscle isolated from the decellularized heart were then transplanted into recipient pigs. After transplantation, the function of the graft was analyzed through echocardiography. A histological analysis was performed to evaluate the postoperative features of the decellularized graft.

Results

The decellularized graft was successfully transplanted in all cases but one. The remaining grafts maintained their morphology and function. They did not exhibit mitral regurgitation or stenosis. Only one animal survived for 3 weeks, and a histological analysis was able to be performed in this case. The transplanted valve was re-covered with endothelial cells. The microvessels in the papillary muscle were recellularized with vascular endothelial cells, and the papillary muscle was completely attached to the papillary muscle of the recipient.

Conclusion

The early outcome of decellularized mitral graft transplantation was acceptable. This native organ-derived acellular scaffold is a promising candidate for the replacement of the mitral valve complex.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Masuda M, Endo S, Natsugoe S, Shimizu H, Doki Y, Hirata Y, et al. Thoracic and cardiovascular surgery in Japan during 2015: annual report by The Japanese Association for Thoracic Surgery. Gen Thorac Cardiovasc Surg. 2018;66(10):581–615.

    Article  Google Scholar 

  2. Lazam S, Vanoverschelde JL, Tribouilloy C, Grigioni F, Suri RM, Avierinos JF, et al. Twenty-year outcome after mitral repair versus replacement for severe degenerative mitral regurgitation: analysis of a large, prospective, multicenter international registry. Circulation. 2017;135(5):410–22.

    Article  Google Scholar 

  3. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials. 2011;32(12):3233–43.

    Article  CAS  Google Scholar 

  4. Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nat Med. 2008;14(2):213–21.

    Article  CAS  Google Scholar 

  5. Weymann A, Loganathan S, Takahashi H, Schies C, Claus B, Hirschberg K, et al. Development and evaluation of a perfusion decellularization porcine heart model. Circ J. 2011;75(4):852–60.

    Article  Google Scholar 

  6. Momtahan N, Sukavaneshvar S, Roeder BL, Cook AD. Strategies and processes to decellularize and recellularize hearts to generate functional organs and reduce the risk of thrombosis. Tissue Eng Part B Rev. 2015;21(1):115–32.

    Article  Google Scholar 

  7. Kitahara H, Yagi H, Tajima K, Okamoto K, Yoshitake A, Aeba R, et al. Heterotopic transplantation of a decellularized and recellularized whole porcine heart. Interact Cardiovasc Thorac Surg. 2016;22(5):571–9.

    Article  Google Scholar 

  8. Yagi H, Fukumitsu K, Fukuda K, Kitago M, Shinoda M, Obara H, et al. Human-scale whole-organ bioengineering for liver transplantation: a regenerative medicine approach. Cell Transplant. 2013;22(2):231–42.

    Article  Google Scholar 

  9. Katsuki Y, Yagi H, Okitsu T, Kitago M, Tajima K, Kadota Y, et al. Endocrine pancreas engineered using porcine islets and partial pancreatic scaffolds. Pancreatology. 2016;16(5):922–30.

    Article  CAS  Google Scholar 

  10. da Costa FDA, Etnel JRG, Charitos EI, Sievers HH, Stierle U, Fornazari D, et al. Decellularized versus standard pulmonary allografts in the ross procedure: propensity-matched analysis. Ann Thorac Surg. 2018;105(4):1205–13.

    Article  Google Scholar 

  11. Etnel JRG, Suss PH, Schnorr GM, Veloso M, Colatusso DF, Balbi Filho EM, et al. Fresh decellularized versus standard cryopreserved pulmonary allografts for right ventricular outflow tract reconstruction during the Ross procedure: a propensity-matched study. Eur J Cardiothorac Surg. 2018;54(3):434–40.

    Article  Google Scholar 

  12. da Costa FDA, Etnel JRG, Torres R, Balbi Filho EM, Torres R, Calixto A, et al. Decellularized allografts for right ventricular outflow tract reconstruction in children. World J Pediatr Congenit Heart Surg. 2017;8(5):605–12.

    Article  Google Scholar 

  13. Iablonskii P, Cebotari S, Ciubotaru A, Sarikouch S, Hoeffler K, Hilfiker A, et al. Decellularized mitral valve in a long-term sheep model. Eur J Cardiothorac Surg. 2018;53(6):1165–72.

    Article  Google Scholar 

  14. Rabkin-Aikawa E, Farber M, Aikawa M, Schoen FJ. Dynamic and reversible changes of interstitial cell phenotype during remodeling of cardiac valves. The Journal of heart valve disease. 2004;13(5):841–7.

    PubMed  Google Scholar 

  15. Rastelli GC. Evaluation of function of mital valve after homotransplantation in the dog. J Thorac Cardiovasc Surg. 1965;49:459–74.

    Article  CAS  Google Scholar 

  16. Osako M, Hattori R, Nakao Y, Yamamura T, Fujii H, Otani H, et al. Freehand cryopreserved mitral valve allograft with flexible ring in the pig. Jpn J Thorac Cardiovasc Surg. 2000;48(12):775–81.

    Article  CAS  Google Scholar 

  17. Acar C, Tolan M, Berrebi A, Gaer J, Gouezo R, Chauvaud S, et al. Homograft replacemnet of the mitral valve, Graft selection, technique of implantation, and result in 43 patients. J Thorac Cardiovasc Surg. 1994;111:367–80.

    Article  Google Scholar 

  18. Shaddy RE, Hunter DD, Osbom KA, Lambert LM, Minich LL, Hawkins JA, et al. Prospective analysis of HLA immunogenicity of cryopreserved valved allografts used in pediatric heart surgery. Circulation. 1996;94(5):1063–7.

    Article  CAS  Google Scholar 

  19. Roger JF, Baskett MA, Maurice A, Nanton MB, Andrew E, Warren MS, et al. Human leukocyte antigen-DR and ABO mismatch are associated with accelerated homograft valve failure in children: Implication for therapeutic interventions. J Thorac Cardiovasc Surg. 2003;126(1):232–8.

    Article  Google Scholar 

  20. Ueno T, Ozawa H, Taira M, Kanaya T, Toda K, Kuratani T, et al. Pulmonary valve replacement with fresh decellularized pulmonary allograft for pulmonary regurgitation after tetralogy of fallot repair- first case report in Japan. Circ J. 2016;80(4):1041–3.

    Article  Google Scholar 

  21. Sarikouch S, Horke A, Tudorache I, Beerbaum P, Westhoff-Bleck M, Boethig D, et al. Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience. Eur J Cardiothorac Surg. 2016;50(2):281–90.

    Article  Google Scholar 

  22. Neumann A, Sarikouch S, Breymann T, Cebotari S, Boethig D, Horke A, et al. Early systemic cellular immune response in children and young adults receiving decellularized fresh allografts for pulmonary valve replacement. Tissue Eng Part A. 2014;20(5–6):1003–111.

    Article  CAS  Google Scholar 

  23. Kneib C, von Glehn CQ, Costa FD, Costa MT, Susin MF. Evaluation of humoral immune response to donor HLA after implantation of cellularized versus decellularized human heart valve allografts. Tissue Antigens. 2012;80(2):165–74.

    Article  CAS  Google Scholar 

  24. Grabow N. Mechanical and structual properties of a novel hybrid heart valve scaffold for tissue engineering. Artif Organs. 2004;28(11):971–9.

    Article  CAS  Google Scholar 

  25. Roy S, Silacci P, Stergiopulos N. Biomechanical properties of decellularized porcine common carotid arteries. Am J Physiol Heart Circ Physiol. 2005;289(4):H1567–1576.

    Article  CAS  Google Scholar 

  26. Mirsadraee S. Development and characterization of an acellular human pericardial Matrix for tissue engineering. Tissue Eng. 2006;12(4):763–73.

    Article  CAS  Google Scholar 

  27. Momtahan N, Poornejad N, Struk JA, Castleton AA, Herrod BJ, Vance BR, et al. Automation of pressure control improves whole porcine heart decellularization. Tissue Eng Part C Methods. 2015;21(11):1148–61.

    Article  CAS  Google Scholar 

  28. Robertson MJ, Dries-Devlin JL, Kren SM, Burchfield JS, Taylor DA. Optimizing recellularization of whole decellularized heart extracellular matrix. PLoS ONE. 2014;9(2):e90406.

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank Hitoshi Inoue and Shintaro Hashiba from Sasazuka Animal Clinic; Yosuke Kawahira and Shingo Sato from the Division of Clinical Engineering; Toshio Otake, Koji Matsumoto and Keiko Kumagai from the Laboratory Animal Center; Shinsuke Shibata, Toshihiro Nagai from the Department of Electron Microscope Laboratory; Naho Murakawa, Rie Kinoshita from the Department of Surgery; So Takasugi, Yusuke Aoki, Tadafumi Tamura and Kaori Katsumata from the Department of Cardiovascular Surgery, School of Medicine, Keio University.

Funding

This work was supported by JSPS KAKENHI Grant number JP 18K08582.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Surgery, Keio University, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan

    Yu Inaba, Yujiro Kawai, Hiroto Kitahara, Tsutomu Ito & Hideyuki Shimizu

  2. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan

    Hiroshi Yagi, Kohei Kuroda & Yuko Kitagawa

  3. Department of Anesthesiology, Keio University, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan

    Jungo Kato

  4. Department of Cardiovascular Surgery, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguroku, Tokyo, 152-8902, Japan

    Mio Kasai & Motohiko Osako

Authors
  1. Yu Inaba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroshi Yagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kohei Kuroda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jungo Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yujiro Kawai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mio Kasai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroto Kitahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tsutomu Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Motohiko Osako
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yuko Kitagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hideyuki Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroshi Yagi.

Ethics declarations

Conflict of interest

Yu Inaba and the other co-authors have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (JPG 150 kb)

Supplementary file2 (MP4 7213 kb)

Supplementary file3 (MP4 5112 kb)

Supplementary file4 (MP4 7621 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Inaba, Y., Yagi, H., Kuroda, K. et al. Transplantation of a decellularized mitral valve complex in pigs. Surg Today 50, 298–306 (2020). https://doi.org/10.1007/s00595-019-01869-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-019-01869-8

Keywords

Search

Navigation