Orthotopic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cells
Abstract Whole lung engineering and the transplantation of its products is an ambitious goal and ultimately a viable solution for alleviating the donor-shortage crisis for lung transplants. There are several limitations currently impeding progress in the field with a major obstacle being efficient r...
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| Format: | Article |
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Nature Portfolio
2024-04-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-57084-0 |
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| author | Fumiko Tomiyama Takaya Suzuki Tatsuaki Watanabe Jun Miyanaga Anna Suzuki Takayasu Ito Sho Murai Yuyo Suzuki Hiromichi Niikawa Hisashi Oishi Hirotsugu Notsuda Yui Watanabe Takashi Hirama Ken Onodera Takeo Togo Masafumi Noda Thomas K. Waddell Golnaz Karoubi Yoshinori Okada |
| author_facet | Fumiko Tomiyama Takaya Suzuki Tatsuaki Watanabe Jun Miyanaga Anna Suzuki Takayasu Ito Sho Murai Yuyo Suzuki Hiromichi Niikawa Hisashi Oishi Hirotsugu Notsuda Yui Watanabe Takashi Hirama Ken Onodera Takeo Togo Masafumi Noda Thomas K. Waddell Golnaz Karoubi Yoshinori Okada |
| author_sort | Fumiko Tomiyama |
| collection | DOAJ |
| description | Abstract Whole lung engineering and the transplantation of its products is an ambitious goal and ultimately a viable solution for alleviating the donor-shortage crisis for lung transplants. There are several limitations currently impeding progress in the field with a major obstacle being efficient revascularization of decellularized scaffolds, which requires an extremely large number of cells when using larger pre-clinical animal models. Here, we developed a simple but effective experimental pulmonary bioengineering platform by utilizing the lung as a scaffold. Revascularization of pulmonary vasculature using human umbilical cord vein endothelial cells was feasible using a novel in-house developed perfusion-based bioreactor. The endothelial lumens formed in the peripheral alveolar area were confirmed using a transmission electron microscope. The quality of engineered lung vasculature was evaluated using box-counting analysis of histological images. The engineered mouse lungs were successfully transplanted into the orthotopic thoracic cavity. The engineered vasculature in the lung scaffold showed blood perfusion after transplantation without significant hemorrhage. The mouse-based lung bioengineering system can be utilized as an efficient ex-vivo screening platform for lung tissue engineering. |
| first_indexed | 2024-04-24T12:39:17Z |
| format | Article |
| id | doaj.art-52c96afc31ac441187e69c4ada4801ca |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T12:39:17Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-52c96afc31ac441187e69c4ada4801ca2024-04-07T11:19:10ZengNature PortfolioScientific Reports2045-23222024-04-0114111210.1038/s41598-024-57084-0Orthotopic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cellsFumiko Tomiyama0Takaya Suzuki1Tatsuaki Watanabe2Jun Miyanaga3Anna Suzuki4Takayasu Ito5Sho Murai6Yuyo Suzuki7Hiromichi Niikawa8Hisashi Oishi9Hirotsugu Notsuda10Yui Watanabe11Takashi Hirama12Ken Onodera13Takeo Togo14Masafumi Noda15Thomas K. Waddell16Golnaz Karoubi17Yoshinori Okada18Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityInstitute of Fluid Science, Tohoku UniversityInstitute of Fluid Science, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityLatner Thoracic Research Laboratories, Toronto General Hospital Research Institute, University Health NetworkLatner Thoracic Research Laboratories, Toronto General Hospital Research Institute, University Health NetworkDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityAbstract Whole lung engineering and the transplantation of its products is an ambitious goal and ultimately a viable solution for alleviating the donor-shortage crisis for lung transplants. There are several limitations currently impeding progress in the field with a major obstacle being efficient revascularization of decellularized scaffolds, which requires an extremely large number of cells when using larger pre-clinical animal models. Here, we developed a simple but effective experimental pulmonary bioengineering platform by utilizing the lung as a scaffold. Revascularization of pulmonary vasculature using human umbilical cord vein endothelial cells was feasible using a novel in-house developed perfusion-based bioreactor. The endothelial lumens formed in the peripheral alveolar area were confirmed using a transmission electron microscope. The quality of engineered lung vasculature was evaluated using box-counting analysis of histological images. The engineered mouse lungs were successfully transplanted into the orthotopic thoracic cavity. The engineered vasculature in the lung scaffold showed blood perfusion after transplantation without significant hemorrhage. The mouse-based lung bioengineering system can be utilized as an efficient ex-vivo screening platform for lung tissue engineering.https://doi.org/10.1038/s41598-024-57084-0Lung bioengineeringVascular engineeringDecellularizationPerfusion-based BioreactorTransplantationBox-counting analysis |
| spellingShingle | Fumiko Tomiyama Takaya Suzuki Tatsuaki Watanabe Jun Miyanaga Anna Suzuki Takayasu Ito Sho Murai Yuyo Suzuki Hiromichi Niikawa Hisashi Oishi Hirotsugu Notsuda Yui Watanabe Takashi Hirama Ken Onodera Takeo Togo Masafumi Noda Thomas K. Waddell Golnaz Karoubi Yoshinori Okada Orthotopic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cells Scientific Reports Lung bioengineering Vascular engineering Decellularization Perfusion-based Bioreactor Transplantation Box-counting analysis |
| title | Orthotopic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cells |
| title_full | Orthotopic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cells |
| title_fullStr | Orthotopic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cells |
| title_full_unstemmed | Orthotopic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cells |
| title_short | Orthotopic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cells |
| title_sort | orthotopic transplantation of the bioengineered lung using a mouse scale perfusion based bioreactor and human primary endothelial cells |
| topic | Lung bioengineering Vascular engineering Decellularization Perfusion-based Bioreactor Transplantation Box-counting analysis |
| url | https://doi.org/10.1038/s41598-024-57084-0 |
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