Tani Kengo, Kimura Daisuke, Asano Yoshiya, Song Cheng-Yang, Shimoda Hiroshi, Minakawa Masahito
Department of Thoracic and Cardiovascular Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
Department of Neuroanatomy, Cell Biology and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
Artif Organs. 2025 May;49(5):778-789. doi: 10.1111/aor.14947. Epub 2025 Jan 16.
Impairment of the visceral pleura following thoracic surgery often leads to air leaks and intrathoracic adhesions. For preventing such complications, mesothelial cell proliferation at the pleural defects can be effective. To develop new materials for pleural defects restoration, we constructed a hybrid artificial pleural tissue (H-APLT) combining polyglycolic acid (PGA) nanofiber sheets with a three-dimensional culture of mesothelial cells and fibroblasts and evaluated its therapeutic efficacy in a rat pleural defect model.
After rat lungs were harvested, pleural mesothelial cells and lung fibroblasts were cultured separately. To construct H-APLT, the cells were then coated with multiple layers of fibronectin and gelatin, followed by a single layer of mesothelial cells on top of multiple layers of fibroblasts accumulated onto a collagen-coated PGA nanofiber sheet. Left lateral thoracotomy was performed, and H-APLTs were transplanted into a rat model with pleural defects (N = 8). After 2-12 weeks of transplantation, lung resection and histological analyses were performed.
H-APLTs exhibited a pleural structure with a highly integrated mesothelial layer in vitro. After transplantation, all eight rats survived until sacrifice. At 12 weeks post-transplantation, the mesothelial layer on the lung surface was observed to be without defects with no intrathoracic adhesions detected.
Successful isogenic engraftment of H-APLTs was achieved in a rat model of pleural defects. The combination of accumulated fibroblasts and collagen-coated PGA nanofiber sheets contributed to the maintenance of the mesothelial layer's structure and function, potentially preventing air leaks and intrathoracic adhesions.
胸外科手术后脏层胸膜损伤常导致气胸和胸腔粘连。为预防此类并发症，胸膜缺损处的间皮细胞增殖可能有效。为开发用于修复胸膜缺损的新材料，我们构建了一种混合人工胸膜组织（H-APLT），它将聚乙醇酸（PGA）纳米纤维片与间皮细胞和成纤维细胞的三维培养相结合，并在大鼠胸膜缺损模型中评估了其治疗效果。
收获大鼠肺后，分别培养胸膜间皮细胞和肺成纤维细胞。为构建H-APLT，先将细胞用多层纤连蛋白和明胶包被，然后在堆积于胶原包被的PGA纳米纤维片上的多层成纤维细胞顶部覆盖单层间皮细胞。进行左侧开胸手术，并将H-APLT移植到胸膜缺损的大鼠模型中（N = 8）。移植2 - 12周后，进行肺切除和组织学分析。
H-APLT在体外呈现出具有高度整合间皮层的胸膜结构。移植后，所有8只大鼠均存活至处死。移植后12周，观察到肺表面的间皮层无缺损，未检测到胸腔粘连。
在大鼠胸膜缺损模型中成功实现了H-APLT的同基因植入。堆积的成纤维细胞与胶原包被的PGA纳米纤维片的组合有助于维持间皮层的结构和功能，可能预防气胸和胸腔粘连。
