Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.

Various strategies have been attempted to replace esophageal defects with natural or artificial substitutes using tissue engineering. However, these methods have not yet reached clinical application because of the high risks related to their immunogenicity or insufficient biocompatibility. In this s...

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Main Authors: Yosuke Takeoka, Keitaro Matsumoto, Daisuke Taniguchi, Tomoshi Tsuchiya, Ryusuke Machino, Masaaki Moriyama, Shosaburo Oyama, Tomoyuki Tetsuo, Yasuaki Taura, Katsunori Takagi, Takuya Yoshida, Abdelmotagaly Elgalad, Naoto Matsuo, Masaki Kunizaki, Shuichi Tobinaga, Takashi Nonaka, Shigekazu Hidaka, Naoya Yamasaki, Koichi Nakayama, Takeshi Nagayasu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0211339
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author Yosuke Takeoka
Keitaro Matsumoto
Daisuke Taniguchi
Tomoshi Tsuchiya
Ryusuke Machino
Masaaki Moriyama
Shosaburo Oyama
Tomoyuki Tetsuo
Yasuaki Taura
Katsunori Takagi
Takuya Yoshida
Abdelmotagaly Elgalad
Naoto Matsuo
Masaki Kunizaki
Shuichi Tobinaga
Takashi Nonaka
Shigekazu Hidaka
Naoya Yamasaki
Koichi Nakayama
Takeshi Nagayasu
author_facet Yosuke Takeoka
Keitaro Matsumoto
Daisuke Taniguchi
Tomoshi Tsuchiya
Ryusuke Machino
Masaaki Moriyama
Shosaburo Oyama
Tomoyuki Tetsuo
Yasuaki Taura
Katsunori Takagi
Takuya Yoshida
Abdelmotagaly Elgalad
Naoto Matsuo
Masaki Kunizaki
Shuichi Tobinaga
Takashi Nonaka
Shigekazu Hidaka
Naoya Yamasaki
Koichi Nakayama
Takeshi Nagayasu
author_sort Yosuke Takeoka
collection DOAJ
description Various strategies have been attempted to replace esophageal defects with natural or artificial substitutes using tissue engineering. However, these methods have not yet reached clinical application because of the high risks related to their immunogenicity or insufficient biocompatibility. In this study, we developed a scaffold-free structure with a mixture of cell types using bio-three-dimensional (3D) printing technology and assessed its characteristics in vitro and in vivo after transplantation into rats. Normal human dermal fibroblasts, human esophageal smooth muscle cells, human bone marrow-derived mesenchymal stem cells, and human umbilical vein endothelial cells were purchased and used as a cell source. After the preparation of multicellular spheroids, esophageal-like tube structures were prepared by bio-3D printing. The structures were matured in a bioreactor and transplanted into 10-12-week-old F344 male rats as esophageal grafts under general anesthesia. Mechanical and histochemical assessment of the structures were performed. Among 4 types of structures evaluated, those with the larger proportion of mesenchymal stem cells tended to show greater strength and expansion on mechanical testing and highly expressed α-smooth muscle actin and vascular endothelial growth factor on immunohistochemistry. Therefore, the structure with the larger proportion of mesenchymal stem cells was selected for transplantation. The scaffold-free structures had sufficient strength for transplantation between the esophagus and stomach using silicon stents. The structures were maintained in vivo for 30 days after transplantation. Smooth muscle cells were maintained, and flat epithelium extended and covered the inner surface of the lumen. Food had also passed through the structure. These results suggested that the esophagus-like scaffold-free tubular structures created using bio-3D printing could hold promise as a substitute for the repair of esophageal defects.
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spelling doaj.art-f77ce61bd48347c493aa9e0cd61d2b4a2022-12-21T21:54:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021133910.1371/journal.pone.0211339Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.Yosuke TakeokaKeitaro MatsumotoDaisuke TaniguchiTomoshi TsuchiyaRyusuke MachinoMasaaki MoriyamaShosaburo OyamaTomoyuki TetsuoYasuaki TauraKatsunori TakagiTakuya YoshidaAbdelmotagaly ElgaladNaoto MatsuoMasaki KunizakiShuichi TobinagaTakashi NonakaShigekazu HidakaNaoya YamasakiKoichi NakayamaTakeshi NagayasuVarious strategies have been attempted to replace esophageal defects with natural or artificial substitutes using tissue engineering. However, these methods have not yet reached clinical application because of the high risks related to their immunogenicity or insufficient biocompatibility. In this study, we developed a scaffold-free structure with a mixture of cell types using bio-three-dimensional (3D) printing technology and assessed its characteristics in vitro and in vivo after transplantation into rats. Normal human dermal fibroblasts, human esophageal smooth muscle cells, human bone marrow-derived mesenchymal stem cells, and human umbilical vein endothelial cells were purchased and used as a cell source. After the preparation of multicellular spheroids, esophageal-like tube structures were prepared by bio-3D printing. The structures were matured in a bioreactor and transplanted into 10-12-week-old F344 male rats as esophageal grafts under general anesthesia. Mechanical and histochemical assessment of the structures were performed. Among 4 types of structures evaluated, those with the larger proportion of mesenchymal stem cells tended to show greater strength and expansion on mechanical testing and highly expressed α-smooth muscle actin and vascular endothelial growth factor on immunohistochemistry. Therefore, the structure with the larger proportion of mesenchymal stem cells was selected for transplantation. The scaffold-free structures had sufficient strength for transplantation between the esophagus and stomach using silicon stents. The structures were maintained in vivo for 30 days after transplantation. Smooth muscle cells were maintained, and flat epithelium extended and covered the inner surface of the lumen. Food had also passed through the structure. These results suggested that the esophagus-like scaffold-free tubular structures created using bio-3D printing could hold promise as a substitute for the repair of esophageal defects.https://doi.org/10.1371/journal.pone.0211339
spellingShingle Yosuke Takeoka
Keitaro Matsumoto
Daisuke Taniguchi
Tomoshi Tsuchiya
Ryusuke Machino
Masaaki Moriyama
Shosaburo Oyama
Tomoyuki Tetsuo
Yasuaki Taura
Katsunori Takagi
Takuya Yoshida
Abdelmotagaly Elgalad
Naoto Matsuo
Masaki Kunizaki
Shuichi Tobinaga
Takashi Nonaka
Shigekazu Hidaka
Naoya Yamasaki
Koichi Nakayama
Takeshi Nagayasu
Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.
PLoS ONE
title Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.
title_full Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.
title_fullStr Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.
title_full_unstemmed Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.
title_short Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.
title_sort regeneration of esophagus using a scaffold free biomimetic structure created with bio three dimensional printing
url https://doi.org/10.1371/journal.pone.0211339
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