Heterotopic transplantation of a decellularized and recellularized whole porcine heart

Hiroto Kitahara, Hiroshi Yagi, Kazuki Tajima, Kazuma Okamoto, Akihiro Yoshitake, Ryo Aeba, Mikihiko Kudo, Ichiro Kashima, Shinji Kawaguchi, Akinori Hirano, Mio Kasai, Yuta Akamatsu, Hidetoshi Oka, Yuukou Kitagawa, Hideyuki Shimizu

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

OBJECTIVES One of the final treatments for end-stage heart failure is heart transplantation. However, a shortage of donor hearts has created a long waiting list and limited benefits. Our ultimate goal is to create a whole beating heart fabricated on an organ scaffold for human heart transplantation. Here, we successfully performed the first transplantation using a decellularized whole porcine heart with mesenchymal stem cells. METHODS A porcine heart was harvested following cardiac arrest induced by a high-potassium solution and stored at -80°C for 24 h. The porcine heart was completely decellularized with 1% sodium dodecyl sulphate and 1% Triton X-100 under the control of perfusion pressure (100 mmHg) and maintained at 37°C. A decellularized whole-heart scaffold was sterilized with gamma irradiation. Cultured mesenchymal stem cells were collected and either infused into the ascending aorta or injected directly into the left ventricular wall. Finally, recellularized whole-heart scaffolds were transplanted into pigs under systemic anticoagulation treatment with heparin. Coronary artery angiography of the transplanted heart graft was performed. RESULTS In our decellularization method, all cellular components were removed, preserving the heart extracellular matrix. Heterotopic transplantations were successfully performed using a decellularized heart and a recellularized heart. The scaffolds were well perfused, without bleeding from the surface or anastomosis site. Coronary angiography revealed a patent coronary artery in both scaffolds. The transplanted decellularized heart was harvested on Day 3. Haematoxylin and eosin staining showed thrombosis in the coronary arteries and migrated inflammatory cells. Haematoxylin and eosin staining of the transplanted recellularized heart showed similar findings, with the exception of injected mesenchymal stem cells. CONCLUSIONS To the best of our knowledge, this is the first report of heterotopic transplantation of a decellularized whole porcine heart with mesenchymal stem cells. The scaffolds endured surgical procedures. We detected short-term coronary artery perfusion in the transplanted scaffolds by angiography. Future studies should analyse the histological features of transplanted decellularized scaffolds and optimize the system for recellularization to apply this unique technology clinically.

Original languageEnglish
Pages (from-to)571-579
Number of pages9
JournalInteractive Cardiovascular and Thoracic Surgery
Volume22
Issue number5
DOIs
Publication statusPublished - 2016 May 1

Fingerprint

Heterotopic Transplantation
Swine
Mesenchymal Stromal Cells
Coronary Vessels
Heart Transplantation
Hematoxylin
Eosine Yellowish-(YS)
Coronary Angiography
Perfusion
Staining and Labeling
Induced Heart Arrest
Waiting Lists
Octoxynol

Keywords

  • Cell transplantation
  • Coronary artery angiography
  • Decellularization
  • Heterotopic transplantation
  • Organ engineering
  • Regenerative therapy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

Heterotopic transplantation of a decellularized and recellularized whole porcine heart. / Kitahara, Hiroto; Yagi, Hiroshi; Tajima, Kazuki; Okamoto, Kazuma; Yoshitake, Akihiro; Aeba, Ryo; Kudo, Mikihiko; Kashima, Ichiro; Kawaguchi, Shinji; Hirano, Akinori; Kasai, Mio; Akamatsu, Yuta; Oka, Hidetoshi; Kitagawa, Yuukou; Shimizu, Hideyuki.

In: Interactive Cardiovascular and Thoracic Surgery, Vol. 22, No. 5, 01.05.2016, p. 571-579.

Research output: Contribution to journalArticle

Kitahara, H, Yagi, H, Tajima, K, Okamoto, K, Yoshitake, A, Aeba, R, Kudo, M, Kashima, I, Kawaguchi, S, Hirano, A, Kasai, M, Akamatsu, Y, Oka, H, Kitagawa, Y & Shimizu, H 2016, 'Heterotopic transplantation of a decellularized and recellularized whole porcine heart', Interactive Cardiovascular and Thoracic Surgery, vol. 22, no. 5, pp. 571-579. https://doi.org/10.1093/icvts/ivw022
Kitahara, Hiroto ; Yagi, Hiroshi ; Tajima, Kazuki ; Okamoto, Kazuma ; Yoshitake, Akihiro ; Aeba, Ryo ; Kudo, Mikihiko ; Kashima, Ichiro ; Kawaguchi, Shinji ; Hirano, Akinori ; Kasai, Mio ; Akamatsu, Yuta ; Oka, Hidetoshi ; Kitagawa, Yuukou ; Shimizu, Hideyuki. / Heterotopic transplantation of a decellularized and recellularized whole porcine heart. In: Interactive Cardiovascular and Thoracic Surgery. 2016 ; Vol. 22, No. 5. pp. 571-579.
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AU - Okamoto, Kazuma

AU - Yoshitake, Akihiro

AU - Aeba, Ryo

AU - Kudo, Mikihiko

AU - Kashima, Ichiro

AU - Kawaguchi, Shinji

AU - Hirano, Akinori

AU - Kasai, Mio

AU - Akamatsu, Yuta

AU - Oka, Hidetoshi

AU - Kitagawa, Yuukou

AU - Shimizu, Hideyuki

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N2 - OBJECTIVES One of the final treatments for end-stage heart failure is heart transplantation. However, a shortage of donor hearts has created a long waiting list and limited benefits. Our ultimate goal is to create a whole beating heart fabricated on an organ scaffold for human heart transplantation. Here, we successfully performed the first transplantation using a decellularized whole porcine heart with mesenchymal stem cells. METHODS A porcine heart was harvested following cardiac arrest induced by a high-potassium solution and stored at -80°C for 24 h. The porcine heart was completely decellularized with 1% sodium dodecyl sulphate and 1% Triton X-100 under the control of perfusion pressure (100 mmHg) and maintained at 37°C. A decellularized whole-heart scaffold was sterilized with gamma irradiation. Cultured mesenchymal stem cells were collected and either infused into the ascending aorta or injected directly into the left ventricular wall. Finally, recellularized whole-heart scaffolds were transplanted into pigs under systemic anticoagulation treatment with heparin. Coronary artery angiography of the transplanted heart graft was performed. RESULTS In our decellularization method, all cellular components were removed, preserving the heart extracellular matrix. Heterotopic transplantations were successfully performed using a decellularized heart and a recellularized heart. The scaffolds were well perfused, without bleeding from the surface or anastomosis site. Coronary angiography revealed a patent coronary artery in both scaffolds. The transplanted decellularized heart was harvested on Day 3. Haematoxylin and eosin staining showed thrombosis in the coronary arteries and migrated inflammatory cells. Haematoxylin and eosin staining of the transplanted recellularized heart showed similar findings, with the exception of injected mesenchymal stem cells. CONCLUSIONS To the best of our knowledge, this is the first report of heterotopic transplantation of a decellularized whole porcine heart with mesenchymal stem cells. The scaffolds endured surgical procedures. We detected short-term coronary artery perfusion in the transplanted scaffolds by angiography. Future studies should analyse the histological features of transplanted decellularized scaffolds and optimize the system for recellularization to apply this unique technology clinically.

AB - OBJECTIVES One of the final treatments for end-stage heart failure is heart transplantation. However, a shortage of donor hearts has created a long waiting list and limited benefits. Our ultimate goal is to create a whole beating heart fabricated on an organ scaffold for human heart transplantation. Here, we successfully performed the first transplantation using a decellularized whole porcine heart with mesenchymal stem cells. METHODS A porcine heart was harvested following cardiac arrest induced by a high-potassium solution and stored at -80°C for 24 h. The porcine heart was completely decellularized with 1% sodium dodecyl sulphate and 1% Triton X-100 under the control of perfusion pressure (100 mmHg) and maintained at 37°C. A decellularized whole-heart scaffold was sterilized with gamma irradiation. Cultured mesenchymal stem cells were collected and either infused into the ascending aorta or injected directly into the left ventricular wall. Finally, recellularized whole-heart scaffolds were transplanted into pigs under systemic anticoagulation treatment with heparin. Coronary artery angiography of the transplanted heart graft was performed. RESULTS In our decellularization method, all cellular components were removed, preserving the heart extracellular matrix. Heterotopic transplantations were successfully performed using a decellularized heart and a recellularized heart. The scaffolds were well perfused, without bleeding from the surface or anastomosis site. Coronary angiography revealed a patent coronary artery in both scaffolds. The transplanted decellularized heart was harvested on Day 3. Haematoxylin and eosin staining showed thrombosis in the coronary arteries and migrated inflammatory cells. Haematoxylin and eosin staining of the transplanted recellularized heart showed similar findings, with the exception of injected mesenchymal stem cells. CONCLUSIONS To the best of our knowledge, this is the first report of heterotopic transplantation of a decellularized whole porcine heart with mesenchymal stem cells. The scaffolds endured surgical procedures. We detected short-term coronary artery perfusion in the transplanted scaffolds by angiography. Future studies should analyse the histological features of transplanted decellularized scaffolds and optimize the system for recellularization to apply this unique technology clinically.

KW - Cell transplantation

KW - Coronary artery angiography

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KW - Heterotopic transplantation

KW - Organ engineering

KW - Regenerative therapy

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