Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Medical-Engineering Hybrid Professional Development Program, Nagasaki University, Nagasaki, Japan.
Interact Cardiovasc Thorac Surg. 2022 Mar 31;34(4):660-667. doi: 10.1093/icvts/ivab306.
Cell therapies, such as stem cell suspension injection, are used to treat bronchopleural fistula. Although it is safe and effective, injected cells cannot remain within the bronchioles of the fistula due to cell leakage into the thoracic cavity. Here, we inserted a 'bio plug' into the fistula, produced using cells and a bio-3D printer, to examine the effectiveness of bio plugs for the closure of bronchopleural fistulas, the optimal cell source and the closure mechanism.
Bio plugs were made with mesenchymal stem (stromal) cells derived from bone marrow (MSCBM), fibroblasts and rat lung micro-vessel endothelial cells using a bio-3D printer with different cell mixing ratios. Six groups, according to the presence or absence and the type of bio plugs, were compared. The plugs were inserted into the bronchi of F344 rats. The obstruction ratio and histological and immunohistochemical findings were evaluated.
MSCBM+ rat lung micro-vessel endothelial cell group exhibited a higher obstruction ratio among all groups excluding the MSCBM group (P = 0.039). This group had fibrosis and CD31-positive cells and fewer CD68-positive cells than MSCBM and MSCBM+ fibroblast groups.
Bio plugs with mixed cells, including stem cells, contribute to bronchial closure in the current experimental setting. Endothelial cells effectively maintain the structure in this model. Although bronchial closure for bronchopleural fistula could not be described as clinical conditions were not reproduced, we collected essential data on bronchial closure; however, further experiments are warranted.
细胞疗法，如干细胞混悬液注射，用于治疗支气管胸膜瘘。尽管它是安全有效的，但由于细胞渗漏到胸腔中，注入的细胞无法留在瘘管的细支气管内。在这里，我们将“生物塞”插入瘘管，该生物塞是使用细胞和生物 3D 打印机产生的，以研究生物塞用于闭合支气管胸膜瘘的有效性、最佳细胞来源和闭合机制。
使用生物 3D 打印机，以不同的细胞混合比例，用骨髓（MSCBM）来源的间充质干细胞（基质）、成纤维细胞和大鼠肺微血管内皮细胞制成生物塞。根据生物塞的存在与否和类型，将其分为 6 组进行比较。将塞子插入 F344 大鼠的支气管中，评估阻塞率以及组织学和免疫组织化学发现。
在所有排除 MSCBM 组的组中，MSCBM+大鼠肺微血管内皮细胞组的阻塞率最高（P=0.039）。与 MSCBM 和 MSCBM+成纤维细胞组相比，该组纤维化程度更高，CD31 阳性细胞更多，CD68 阳性细胞更少。
在当前的实验环境中，包含干细胞在内的混合细胞生物塞有助于支气管闭合。内皮细胞在该模型中有效地维持结构。虽然不能将支气管胸膜瘘的支气管闭合描述为复制临床条件，但我们收集了关于支气管闭合的重要数据；然而，还需要进一步的实验。
