Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
School of Communication Sciences and Disorders, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
Cell Transplant. 2024 Jan-Dec;33:9636897241228026. doi: 10.1177/09636897241228026.
No radical treatment is available for the regeneration of dysfunction and defects in airway epithelia. Artificial tracheae made of polypropylene and collagen sponge were used in clinical studies to reconstitute tracheae after resection. For early epithelialization of the luminal surface of the artificial trachea, a model was established, that is, an artificial trachea covered with human-induced pluripotent stem cell-derived airway epithelial cells (hiPSC-AECs) was transplanted into a tracheal defect in an immunodeficient rat. Unlike the cell types of hiPSC-derived cells that are currently used in clinical studies, AECs maintain tissues by proliferation and differentiation of basal cells into various cell types that constitute AECs constantly. Therefore, post-transplantation, the proportion of each cell type, such as ciliated and goblet cells, may change; however, no studies have examined this possibility. In this study, using our hiPSC-AEC-transplanted rat model, we investigated changes in the proportion of each cell type in hiPSC-AECs pre-transplantation and post-transplantation. As a result, the proportion of each cell type changed post-transplantation. The proportion of ciliated, basal, and club cells increased, and the proportion of goblet cells decreased post-transplantation. In addition, the proportion of each cell type in engrafted hiPSC-AECs is more similar to the proportion of each cell type in normal proximal airway tissue than the proportion of each cell type pre-transplantation. The results of this study are useful for the development of therapeutic techniques using hiPSC-AEC transplantation.
目前，尚无有效的方法可用于气道上皮细胞功能障碍和缺陷的再生。在临床研究中，曾使用聚丙烯和胶原海绵制成的人工气管来重建切除后的气管。为了使人工气管的腔面能够早期上皮化，建立了一个模型，即将覆盖有人诱导多能干细胞衍生的气道上皮细胞（hiPSC-AEC）的人工气管移植到免疫缺陷大鼠的气管缺损部位。与目前用于临床研究的 hiPSC 衍生细胞类型不同，AEC 通过基底细胞的增殖和分化为构成 AEC 的各种细胞类型来维持组织。因此，移植后，各种细胞类型（如纤毛细胞和杯状细胞）的比例可能会发生变化；但是，尚无研究对此可能性进行过检验。在这项研究中，我们使用 hiPSC-AEC 移植大鼠模型，研究了移植前和移植后 hiPSC-AEC 中每种细胞类型的比例变化。结果表明，移植后每种细胞类型的比例均发生了变化。移植后，纤毛细胞、基底细胞和 club 细胞的比例增加，杯状细胞的比例减少。此外，与移植前相比，植入的 hiPSC-AEC 中每种细胞类型的比例与正常近端气道组织中每种细胞类型的比例更为相似。这项研究的结果有助于开发使用 hiPSC-AEC 移植的治疗技术。
