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

ABSTRACT: 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 ?-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.

SUBMITTER: Takeoka Y

PROVIDER: S-EPMC6408002 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Takeoka Yosuke Y Matsumoto Keitaro K Taniguchi Daisuke D Tsuchiya Tomoshi T Machino Ryusuke R Moriyama Masaaki M Oyama Shosaburo S Tetsuo Tomoyuki T Taura Yasuaki Y Takagi Katsunori K Yoshida Takuya T Elgalad Abdelmotagaly A Matsuo Naoto N Kunizaki Masaki M Tobinaga Shuichi S Nonaka Takashi T Hidaka Shigekazu S Yamasaki Naoya N Nakayama Koichi K Nagayasu Takeshi T

PloS one 20190308 3

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 transplantati ...[more]

PMID: 30849123

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Project description:Therapeutic options are limited for severe lung injury and disease as the spontaneous regeneration of functional alveolar is terminated owing to the weakness of the inherent stem cells and the dyscrasia of the niche. Umbilical cord mesenchymal-derived stem cells (UC-MSCs) have been applied to clinical trials to promote lung repair through stem cell niche restruction. However, the application of UC-MSCs is hampered by the effectiveness of cell transplantation with few cells homing to the injury sites and poor retention, survival, and proliferation in vivo. In this study, we constructed an artificial three-dimensional (3D) biomimetic scaffold-based MSCs implant to establish a beneficial regeneration niche for endogenous stem cells in situ lung regeneration. The therapeutic potential of 3D biomimetic scaffold-based MSCs implants was evaluated by 3D culture in vitro. And RNA sequencing (RNA-Seq) was mapped to explore the gene expression involved in the niche improvement. Next, a model of partial lung resection was established in rats, and the implants were implanted into the operative region. Effects of the implants on rat resected lung injury repair were detected. The results revealed that UC-MSCs loaded on biomimetic scaffolds exerted strong paracrine effects and some UC-MSCs migrated to the lung from scaffolds and had long-term retention to suppress inflammation and fibrosis in residual lungs and promoted vascular endothelial cells and alveolar type II epithelial cells to enter the scaffolds. Then, under the guidance of the ECM-mimicking structures of scaffolds and the stimulation of the remaining UC-MSCs, vascular and alveolar-like structures were formed in the scaffold region. Moreover, the general morphology of the operative lung was also restored. Taken together, the artificial 3D biomimetic scaffold-based MSCs implants induce in situ lung regeneration and recovery after lung destruction, providing a promising direction for tissue engineering and stem cell strategies in lung regeneration.

Dataset Information

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

Publications

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

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