Batchinsky Andriy I, Roberts Teryn R, Antebi Ben, Necsoiu Corina, Choi Jae H, Herzig Maryanne, Cap Andrew P, McDaniel Jennifer S, Rathbone Christopher R, Chung Kevin K, Cancio Leopoldo C
Autonomous Reanimation and Evacuation Research Program, The Geneva Foundation, San Antonio, Texas.
Maryland Stem Cell Research Fund, Columbia, Maryland.
Am J Respir Crit Care Med. 2023 Dec 15;208(12):1283-1292. doi: 10.1164/rccm.202305-0865OC.
Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Yorkshire swine ( = 32, 44.3 ± 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate ( = 10; 3 × 10 white blood cells and a mean of 56.6 × 10 platelets per dose), allogeneic MSCs ( = 10; 6.1 × 10 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals ( = 12). The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 ± 10 h) versus control animals (14 ± 2 h) ( = 0.004), reduced ARDS severity at 24 ( < 0.001) and 48 ( = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-α (tumor necrosis factor-α). The intravenous administration of three doses of freshly processed autologous bone marrow-derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.
急性呼吸窘迫综合征（ARDS）损伤后早期缓解策略匮乏。同种异体基质细胞治疗在ARDS发生后进行，需要专业技术和设备，且迄今为止显示的益处有限。评估损伤后立即静脉注射自体或同种异体骨髓间充质基质细胞（MSCs）治疗因烟雾吸入和烧伤导致的急性呼吸窘迫综合征（ARDS）的疗效。约克郡猪（n = 32，体重44.3±0.5千克）接受静脉麻醉、置管、严重烟雾吸入和40%体表面积火焰烧伤，随后在重症监护病房（ICU）接受72小时的全天候护理。进行机械通气、补液、使用升压药、通过支气管镜清除痂皮、每日进行肺部计算机断层扫描以及动脉血液检测。损伤后以及24小时和48小时后，将动物随机分为三组，分别接受自体浓缩骨髓抽吸物（n = 10；每剂含3×10⁹白细胞和平均56.6×10⁹血小板）、从健康供体猪采集的同种异体MSCs（n = 10；每剂含6.1×10⁶ MSCs），或损伤对照组动物不进行治疗（n = 12）。损伤后以及24小时和48小时静脉注射MSCs可使接受自体MSCs治疗的猪（48±10小时）与对照组动物（14±2小时）相比ARDS发病延迟（P = 0.004），在24小时（P < 0.001）和48小时（P = 0.003）时降低ARDS严重程度，并且在计算机断层扫描上显示实变明显减轻（差异无统计学意义）。72小时时自体组10只中有1只（10%）死亡，同种异体组10只中有5只（50%）死亡，损伤对照组动物12只中有6只（50%）死亡（差异无统计学意义）。自体和同种异体MSCs均抑制肿瘤坏死因子-α（TNF-α）的全身浓度。静脉注射三剂新鲜处理的自体骨髓来源MSCs可延迟猪ARDS的发展并降低其严重程度。在猪中床边采集和注射自体MSCs是可行的，可能是一种可行的ARDS损伤缓解策略。
