The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases, Pittsburgh, Pennsylvania, USA.
Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
BMJ Open Respir Res. 2019 Jan 12;6(1):e000308. doi: 10.1136/bmjresp-2018-000308. eCollection 2019.
Bone marrow-derived multipotent adult progenitor cells (MAPCs) are adult allogeneic adherent stem cells currently investigated clinically for use in acute respiratory distress syndrome (ARDS). To date, there is no agreement on which is the best method for stem cells delivery in ARDS. Here, we compared the efficacy of two different methods of administration and biodistribution of MAPC for the treatment of ARDS in a sheep model.
MAPC were labelled with [F] fluoro-29-deoxy-D-glucose and delivered by endobronchial (EB) or intravenous route 1 hour after lipopolysaccharide infusion in sheep mechanically ventilated. PET/CT images were acquired to determine the biodistribution and retention of the cells at 1 and 5 hours of administration.
The distribution and retention of the MAPC was dependent on the method of cell administration. By EB route, PET images showed that MAPC remained at the site of administration and no changes were observed after 5 hours, whereas with intravenous route, the cells had broad biodistribution to different organs, being the lung the main organ of retention at 1 and 5 hours. MAPC demonstrated an equal effect on arterial oxygenation recovery by either route of administration.
The EB or intravenous routes of administration of MAPC are both effective for the treatment of ARDS in an acute sheep model, and the effect of MAPC therapy is not dependent of parenchymal integration or systemic biodistribution.
骨髓来源的多能成体祖细胞（MAPC）是目前正在临床研究中用于治疗急性呼吸窘迫综合征（ARDS）的异基因贴壁干细胞。迄今为止，对于 ARDS 中干细胞输送的最佳方法尚无共识。在此，我们比较了两种不同给药方式和 MAPC 生物分布对绵羊急性呼吸窘迫综合征模型的治疗效果。
在绵羊机械通气的情况下，脂多糖输注 1 小时后，通过支气管内（EB）或静脉途径给予标记有[F]氟-29-脱氧-D-葡萄糖的 MAPC。进行 PET/CT 扫描以确定给药 1 和 5 小时时细胞的生物分布和保留情况。
MAPC 的分布和保留取决于细胞给药方式。通过 EB 途径，PET 图像显示 MAPC 保留在给药部位，5 小时后无变化，而通过静脉途径，细胞广泛分布到不同器官，肺是 1 小时和 5 小时时主要的保留器官。通过两种给药途径，MAPC 对动脉氧合恢复的效果均相同。
在急性绵羊模型中，MAPC 的 EB 或静脉给药途径均可有效治疗 ARDS，并且 MAPC 治疗的效果与实质整合或全身生物分布无关。
