Mizuno Keisuke, Ohnishi Hiroe, Kishimoto Yo, Okuyama Hideaki, Kawai Yoshitaka, Kitano Masayuki, Hayashi Yasuyuki, Omori Koichi
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Cell Reprogram. 2024 Dec;26(6):156-163. doi: 10.1089/cell.2024.0054. Epub 2024 Nov 27.
Tracheal reconstruction is necessary in patients with large tracheal defects. Previously, artificial tracheae made of polypropylene and collagen sponge have been used clinically by our group. As a basic research aimed at promoting epithelialization for infection defense, we transplanted cell sheets of human induced pluripotent stem cell (hiPSC)-derived airway epithelial cells (iAECs) with artificial tracheae into tracheal defects of rats and confirmed their engraftment. In this study, we examined the difference in the cell engraftment between hiPSC-derived airway epithelial progenitor cells (iAEPCs) and iAECs. Cell sheets were collected on days 38, 45, and 56 of induction into iAECs, then transplanted into nude rats with tracheal defects along with the artificial trachea. Two weeks after transplantation, surviving human nuclear antigen (HNA)-positive epithelial cells were observed none of six rats in the 38-day group, two out of six in 45-day group, and five out of six in the 56-day group. The proportion of surviving HNA+ cells among the epithelial cells of 56-day group was significantly higher those of 38-day group. Differentiated iAECs are more suitable for the transplantation of hiPSCs into tracheal defects. Our findings propose the use of differentiated cells for improvement of engraftment efficiency.
对于存在大的气管缺损的患者，气管重建是必要的。此前，我们团队已在临床上使用由聚丙烯和胶原海绵制成的人工气管。作为一项旨在促进上皮化以抵御感染的基础研究，我们将人诱导多能干细胞（hiPSC）来源的气道上皮细胞（iAECs）的细胞片与人工气管一起移植到大鼠的气管缺损处，并证实了它们的植入。在本研究中，我们检测了hiPSC来源的气道上皮祖细胞（iAEPCs）和iAECs在细胞植入方面的差异。在诱导成为iAECs的第38天、45天和56天收集细胞片，然后将其与人工气管一起移植到有气管缺损的裸鼠体内。移植两周后，在38天组的6只大鼠中未观察到存活的人核抗原（HNA）阳性上皮细胞，45天组的6只中有2只，56天组的6只中有5只。56天组上皮细胞中存活的HNA+细胞比例显著高于38天组。分化的iAECs更适合将hiPSCs移植到气管缺损处。我们的研究结果建议使用分化细胞来提高植入效率。
