Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Thoracic Surgery, The University of Tokyo Hospital, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Semin Thorac Cardiovasc Surg. 2022 Summer;34(2):752-759. doi: 10.1053/j.semtcvs.2021.03.006. Epub 2021 Mar 11.
Lung transplantation is the only treatment for end-stage lung disease; however, donor organ shortage and intense immunosuppression limit its broad clinical impact. Bioengineering of lungs with patient-derived cells could overcome these problems. We created bioartificial lungs by seeding human-derived cells onto porcine lung matrices and performed orthotopic transplantation to assess feasibility and in vivo function. Porcine decellularized lung scaffolds were seeded with human airway epithelial cells and human umbilical vein endothelial cells. Following in vitro culture, the bioartificial lungs were orthotopically transplanted into porcine recipients with planned 1-day survival (n = 3). Lungs were assessed with histology and in vivo function. Orthotopic transplantation of cadaveric lungs was performed as control. Engraftment of endothelial and epithelial cells in the grafts were histologically demonstrated. Technically successful orthotopic anastomoses of the vasculatures and airway were achieved in all animals. Perfusion and ventilation of the lung grafts were confirmed intraoperatively. The gas exchange function was evident immediately after transplantation; PO gradient between pulmonary artery and vein were 178 ± 153 mm Hg in the bioartificial lung group and 183 ± 117 mm Hg in the control group. At time of evaluation 24 hours after reperfusion, the pulmonary arteries were found to be occluded with thrombus in all bioartificial lungs. Engineering and orthotopic transplantation of bioartificial lungs with human cells were technically feasible in a porcine model. Early gas exchange function was evident. Further progress in optimizing recellularization and maturation of the grafts will be necessary for sustained perfusability and function.
肺移植是治疗终末期肺病的唯一方法；然而，供体器官短缺和强烈的免疫抑制限制了其广泛的临床影响。用患者来源的细胞对肺进行生物工程改造可以克服这些问题。我们通过将人源性细胞接种到猪肺基质上来创建生物人工肺，并进行了原位移植以评估其可行性和体内功能。猪去细胞化的肺支架被人呼吸道上皮细胞和人脐静脉内皮细胞接种。体外培养后，将生物人工肺原位移植到计划 1 天存活的猪受体中（n=3）。用组织学和体内功能评估肺。进行尸体供肺的原位移植作为对照。在移植物中观察到内皮细胞和上皮细胞的植入。所有动物均成功完成了血管和气道的原位吻合术。术中确认了肺移植物的灌注和通气。移植后立即出现气体交换功能；生物人工肺组肺动脉和静脉之间的 PO 梯度为 178±153mmHg，对照组为 183±117mmHg。在再灌注后 24 小时评估时，发现所有生物人工肺中的肺动脉均被血栓阻塞。用人类细胞对生物人工肺进行工程和原位移植在猪模型中是可行的。早期的气体交换功能是明显的。进一步优化移植物的再细胞化和成熟将是维持可灌注性和功能所必需的。
