Immunoregulatory effects of multipotent adult progenitor cells in a porcine ex vivo lung perfusion model
Immunoregulatory effects of multipotent adult progenitor cells in a porcine ex vivo lung perfusion model
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DOI：
10.1186/s13287-017-0603-5
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发表时间：
2017-07-05
影响因子：
7.5
通讯作者：
Neyrinck, Arne P.
中科院分区：
文献类型：
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作者：
Martens, An;Ordies, Sofie;Neyrinck, Arne P.
背景资料：原发性移植物功能障碍（PGD）被认为是移植后针对新肺同种异体移植物的炎症反应的最终结果。先前的研究表明，MAPC细胞疗法可能会通过其对促炎/抗炎平衡的旁分泌作用来减轻这种损伤。本研究旨在探讨MAPC细胞在PGD中的免疫调节能力，当在airways.Methods：家猪肺（n = 6/组）进行了90分钟的热缺血。将肺冷冲洗，在冰上插管并置于EVLP上6小时。在EVLP开始时，将40 ml白蛋白-plasmalyte混合物分布在气道中（对照组）。在MAPC细胞组中，将1.5亿个MAPC细胞（ReGenesys/Athersys，Cleveland，OH，USA）加入该混合物中。EVLP结束时进行肺血管阻力、肺顺应性、PaO 2/FiO（2）、湿干重比（W/D）采样和支气管肺泡灌洗（BAL）（2 x 30 ml）多重分析。在MAPC细胞组中，BAL嗜中性粒细胞显著减少。此外，有一个显着减少TNF-α，IL-1 β和IFN-γ在BAL，但不是在IFN-α，而IL-4，IL-10和IL-8低于检测limit.Conclusions：虽然没有生理效应的MAPC细胞分布在气道EVLP期间检测，我们观察到减少促炎细胞因子和中性粒细胞在BAL中的MAPC细胞组。这种对先天免疫系统的影响可能在移植后严重改变PGD过程中发挥重要作用。进一步的实验将阐明MAPC细胞给药对移植后移植物功能的免疫调节作用。
Background: Primary graft dysfunction (PGD) is considered to be the end result of an inflammatory response targeting the new lung allograft after transplant. Previous research has indicated that MAPC cell therapy might attenuate this injury by its paracrine effects on the pro-/anti-inflammatory balance. This study aims to investigate the immunoregulatory capacities of MAPC cells in PGD when administered in the airways.Methods: Lungs of domestic pigs (n = 6/group) were subjected to 90 minutes of warm ischemia. Lungs were cold flushed, cannulated on ice and placed on EVLP for 6 hours. At the start of EVLP, 40 ml of an albumin-plasmalyte mixture was distributed in the airways (CONTR group). In the MAPC cell group, 150 million MAPC cells (ReGenesys/Athersys, Cleveland, OH, USA) were added to this mixture. At the end of EVLP, a physiological evaluation (pulmonary vascular resistance, lung compliance, PaO2/FiO(2)), wet-to-dry weight ratio (W/D) sampling and a multiplex analysis of bronchoalveolar lavage (BAL) (2 x 30 ml) was performed.Results: Pulmonary vascular resistance, lung compliance, PaO2/FiO(2) and W/D were not statistically different at the end of EVLP between both groups. BAL neutrophilia was significantly reduced in the MAPC cell group. Moreover, there was a significant decrease in TNF-alpha, IL-1 beta and IFN-gamma in the BAL, but not in IFN-alpha; whereas IL-4, IL-10 and IL-8 were below the detection limit.Conclusions: Although no physiologic effect of MAPC cell distribution in the airways was detected during EVLP, we observed a reduction in pro-inflammatory cytokines and neutrophils in BAL in the MAPC cell group. This effect on the innate immune system might play an important role in critically modifying the process of PGD after transplantation. Further experiments will have to elucidate the immunoregulatory effect of MAPC cell administration on graft function after transplantation.