Tan Qiang, Liu Ruijun, Chen Xiaoke, Wu Jingxiang, Pan Yinggen, Lu Shun, Weder Walter, Luo Qingquan
Shanghai Lung Cancer Center, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, China.
Department of Anesthesia, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, China.
J Thorac Dis. 2017 Jan;9(1):22-29. doi: 10.21037/jtd.2017.01.50.
Delayed revascularization process and substitute infection remain to be key challenges in tissue engineered (TE) airway reconstruction. We propose an " bioreactor" design, defined as an implanted TE substitutes perfused with an intra-scaffold medium flow created by an extracorporeal portable pump system for organ regeneration. The perfusate keeps pre-seeded cells alive before revascularization. Meanwhile the antibiotic inside the perfusate controls topical infection.
A stage IIIA squamous lung cancer patient received a 5-cm TE airway substitute, bridging left basal segment bronchus to carina, with the bioreactor design to avoid left pneumonectomy. Continuous intra-scaffold Ringer's-gentamicin perfusion lasted for 1 month, together with orthotopic peripheral total nucleated cells (TNCs) injection twice a week.
The patient recovered uneventfully. Bronchoscopy follow-up confirmed complete revascularization and reepithelialization four months postoperatively. Perfusate waste test demonstrated various revascularization growth factors secreted by TNCs. The patient received two cycles of chemotherapy and 30 Gy radiotherapy thereafter without complications related to the TE substitute.
bioreactor design combines the traditionally separated 3D cell-scaffold culture system and the regenerative processes associated with TE substitutes, while treating the recipients as bioreactors for their own TE prostheses. This design can be applied clinically. We also proved for the first time that TE airway substitute is able to tolerate chemo-radiotherapy and suitable to be used in cancer treatment.
延迟血管化过程和替代物感染仍然是组织工程（TE）气道重建中的关键挑战。我们提出一种“生物反应器”设计，定义为一种植入式TE替代物，通过体外便携式泵系统产生的支架内介质流进行灌注，以促进器官再生。灌注液在血管化之前保持预先接种的细胞存活。同时，灌注液中的抗生素控制局部感染。
一名IIIA期肺鳞状癌患者接受了一个5厘米的TE气道替代物，将左肺下叶基底段支气管与隆突连接，采用生物反应器设计以避免左肺切除术。持续的支架内林格氏液-庆大霉素灌注持续1个月，同时每周两次原位注射外周全核细胞（TNCs）。
患者顺利康复。支气管镜随访证实术后四个月完全血管化和重新上皮化。灌注液废物检测显示TNCs分泌了多种血管化生长因子。患者此后接受了两个周期的化疗和30 Gy放疗，未出现与TE替代物相关的并发症。
生物反应器设计将传统上分离的3D细胞-支架培养系统与TE替代物相关的再生过程结合起来，同时将接受者视为自身TE假体的生物反应器。这种设计可应用于临床。我们还首次证明TE气道替代物能够耐受放化疗，适合用于癌症治疗。
