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利用受体来源细胞构建的生物工程肺脏移植到大型动物模型中。

Transplantation of Bioengineered Lungs Created From Recipient-Derived Cells Into a Large Animal Model.

机构信息

Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

出版信息

Semin Thorac Cardiovasc Surg. 2021;33(1):263-271. doi: 10.1053/j.semtcvs.2020.03.005. Epub 2020 Apr 27.

Abstract

The use of bioartificial lungs may represent a breakthrough for the treatment of end-stage lung disease. The present study aimed to evaluate the feasibility of transplanting bioengineered lungs created from autologous cells. Porcine decellularized lung scaffolds were seeded with porcine recipient-derived airway and vascular cells. The porcine recipient-derived cells were collected from lung tissue obtained by pulmonary wedge resection. Following culture of autologous cells in the scaffolds, the resulting grafts were unilaterally transplanted into porcine recipients (n = 3). Allograft left unilateral lung transplantation was performed in the control group (n = 3). Left unilateral transplantation of decellularized grafts was also performed in a separate control group (n = 2). In vivo functions were assessed for 2 hours after transplantation. Histologic evaluation and immunostaining showed the presence of airway and vascular cells in the bioengineered lungs. No animals survived in the decellularized transplant group, whereas all animals survived in the bioengineered transplant and allotransplant groups. However, bioengineered lung grafts showed marked bullous changes. The oxygen exchange was comparable between the bioengineered lung graft transplant and allograft transplant groups. However, the carbon dioxide gas exchange of the bioengineered lung graft transplant group was significantly lower than that of the allograft transplant group at 2 hours after transplantation (4.10 ± 0.87 mm Hg vs 24.7 ± 10.1 mm Hg, P = 0.02). Transplantation of bioartificial lung grafts created from autologous cells was feasible in the super-acute phase. However, bullous changes and poor carbon dioxide gas exchange remain limitations of this method.

摘要

生物人工肺的应用可能代表着治疗终末期肺病的一个突破。本研究旨在评估从自体细胞构建的生物工程肺进行移植的可行性。使用猪去细胞肺支架种植猪受体来源的气道和血管细胞。猪受体来源的细胞是从通过肺楔形切除术获得的肺组织中收集的。在支架中培养自体细胞后,将得到的移植物单向移植到猪受体中(n=3)。在对照组(n=3)中进行同种异体左单侧肺移植。在单独的对照组(n=2)中也进行了去细胞移植物的左单侧移植。在移植后 2 小时评估体内功能。组织学评估和免疫染色显示生物工程肺中有气道和血管细胞的存在。去细胞移植组没有动物存活,而生物工程移植组和同种异体移植组所有动物都存活。然而,生物工程肺移植物显示出明显的大疱性改变。在移植后 2 小时,生物工程肺移植物移植组和同种异体移植组的氧交换相当(4.10±0.87mmHg 对 24.7±10.1mmHg,P=0.02)。然而,生物工程肺移植物移植组的二氧化碳气体交换明显低于同种异体移植组(4.10±0.87mmHg 对 24.7±10.1mmHg,P=0.02)。从自体细胞构建的生物人工肺移植物在超急性阶段的移植是可行的。然而,大疱性改变和二氧化碳气体交换不良仍然是该方法的限制。

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