title: Heterotopic transplantation of a decellularized and recellularized whole porcine heart.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kitahara
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan hy0624@gmail.com.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagi
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Tajima
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yoshitake
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Aeba
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kashima
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawaguchi
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hirano
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Kasai
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Akamatsu
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Oka
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006333:Heart Failure / Q000601:surgery*; D016027:Heart Transplantation / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D013552:Swine; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D016042:Transplantation, Heterotopic
keywords: Cell transplantation; Coronary artery angiography; Decellularization; Heterotopic transplantation; Organ engineering; Regenerative therapy