Orthotopic foetal lung tissue direct injection into lung showed a preventive effect against paraquat-induced acute lung injury in mice.

Orthotopic foetal lung tissue direct injection into lung showed a preventive effect against paraquat-induced acute lung injury in mice.
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原位胎儿肺组织直接注射入肺对百草枯引起的小鼠急性肺损伤具有预防作用。

DOI:
10.1093/ejcts/ezaa091
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发表时间:
2020
期刊:
Eur J Cardiothorac Surg
影响因子:
--
通讯作者:
Takebe T
Takebe T
中科院分区:
--
文献类型:
--
作者:
Okabe R;Chen-Yoshikawa TF;Yoshizawa A;Hirashima T;Saito M;Date H;Takebe T

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肺移植是终末期肺病患者唯一有效的治疗方法,但器官短缺危机需要替代疗法的发展。最近的研究强调了胎儿组织移植促进重要器官再生的潜力,如被致命疾病损坏的肝脏。在此,以恢复肺功能为目的,我们假设,同种异体胎儿肺组织植入将减轻严重的respiratory failure. METHODS肺组织从妊娠绿色荧光蛋白-C57 BL/6小鼠在妊娠13.5天的胎儿注射到受体小鼠的左肺。百草枯致大鼠严重肺损伤,观察1个月后存活率及病理组织学改变,结果治疗组存活率为39%,明显高于对照组的5.9%(P= 0.034)。免疫组化染色显示,在胚胎13.5天的胎肺腺样结构中,可见到抗白细胞介素10抗体阳性的胞浆染色细胞。原位植入后4周,苏木精和伊红染色显示肺炎症细胞减少,肺水肿减轻,胎肺细胞的活跃细胞增殖增加。肺损伤评分显示,未成熟胎肺可提高百草枯诱导的重度肺损伤小鼠的存活率,需要进行系统的随访研究。胚胎13.5天胎肺组织中的抗炎细胞因子可能抑制严重的肺损伤。
OBJECTIVESLung transplantation is the only effective therapy for patients with end-stage lung disease but an organ shortage crisis necessitates the development of alternative therapies. Recent studies have highlighted the potential of foetal tissue transplantation to facilitate the regeneration of vital organs such as liver that have been damaged by lethal diseases. Herein, with the aim of restoring pulmonary function, we hypothesized that allogenic foetal lung tissue implantation would attenuate severe respiratory failure.METHODSLung tissue from the foetuses of pregnant green fluorescent protein-C57BL/6 mice at 13.5 days of gestation was injected into the left lungs of recipient mice. Severe lung injury was induced by paraquat, and we analysed the survival rate and pathohistological findings after 1 month.RESULTSThe survival rate of the therapy group was 39%, which was significantly higher than the vehicle group at 5.9% (P= 0.034). Immunochemical staining showed that positive cytoplasmic stained cells with anti-interleukin-10 antibody were identified in the gland-like structure of embryonic day 13.5 foetal lung. At 4 weeks after orthotopic implantation, haematoxylin and eosin staining showed reduced lung inflammatory cells, reduced lung oedema and increased active cell proliferation of foetal lung cells. Lung injury score showed that the airway septal thickening revealed statistically significant differences between vehicle and foetal lung therapy (P< 0.001).CONCLUSIONSImmature foetal lungs improved the survival rate of mice with paraquat-induced severe lung injury, establishing the need for systematic follow-up studies. The anti-inflammatory cytokine in the tissue from embryonic day 13.5 foetal lung might suppress severe lung injury.
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