Department of Otolaryngology, Wake Forest Baptist Health, Winston Salem, North Carolina, USA.
Otolaryngol Head Neck Surg. 2014 Mar;150(3):428-33. doi: 10.1177/0194599813516751. Epub 2013 Dec 23.
Tracheal reconstruction using a stem cell-based engineered trachea has recently shown promise. Our goal is to achieve a single-stage stem cell-based tracheal replacement.
Prospective feasibility study.
Wake Forest Institute of Regenerative Medicine.
Five healthy male beagles were implanted with a 2.5-cm segment of decellularized trachea. A sixth animal, planned for the control arm, died of anesthetic complications prior to tracheal implantation. The remaining 5 beagles were divided into 2 study arms: 4 had adipose-derived stem cells coating the lumen of the donor trachea, and a control animal had the trachea implanted cell free. The donor tracheas were obtained from previously sacrificed size-matched canines and decellularized. The adipose tissue was harvested from a recipient animal and the trachea prepared, seeded, and then implanted, all in one operation. Adipose stem cells were labeled fluorescently.
Five of 6 planned surgical procedures were completed successfully. All required sacrifice for airway distress at approximately 1 week postoperatively. All tracheal grafts were found to be malacic and compromised.
In a canine model using a decellularized tracheal scaffold and adipose stem cells, the postoperative inflammatory response and evidence of rejection was minimal. However, all scaffolds exhibited breakdown, compromising the animals' airways, necessitating euthanasia earlier than planned. For future study, a similar animal model using a single-stage approach with a more robust scaffold may allow for greater survival and stem cell differentiation.
使用基于干细胞的工程化气管进行气管重建最近显示出前景。我们的目标是实现基于干细胞的单阶段气管替代。
前瞻性可行性研究。
维克森林再生医学研究所。
将 5 只健康雄性比格犬植入 2.5 厘米长的脱细胞气管段。第六只动物计划用于对照臂,在气管植入前死于麻醉并发症。其余 5 只比格犬分为 2 个研究组:4 只动物的供体气管腔内涂有脂肪源性干细胞,对照组动物的气管无细胞植入。供体气管取自先前处死的大小匹配的犬,并进行脱细胞处理。从受体动物中采集脂肪组织,并准备、接种和植入气管,所有操作均在一次手术中完成。脂肪干细胞被荧光标记。
计划的 6 次手术中有 5 次成功完成。所有动物均因术后约 1 周出现气道窘迫而需要处死。所有气管移植物均出现软化和受损。
在使用脱细胞气管支架和脂肪干细胞的犬模型中,术后炎症反应和排斥证据最小。然而,所有支架都出现了破裂,使动物的气道受损,需要提前安乐死。为了进一步研究,使用单一阶段方法和更强大的支架的类似动物模型可能允许更大的存活率和干细胞分化。