骨髓干细胞经人白细胞介素 10 修饰可减轻大鼠肺移植急性排斥反应。
Bone marrow stem cells modified with human interleukin 10 attenuate acute rejection in rat lung allotransplantation.
机构信息
Department of General Thoracic Surgery, University Hospital Bern, Bern, Switzerland.
Department of General Thoracic Surgery and Lung Transplantation, Pomeranian Medical University, Szczecin, Poland.
出版信息
Eur J Cardiothorac Surg. 2018 Jan 1;53(1):194-200. doi: 10.1093/ejcts/ezx257.
OBJECTIVES
The aim of this study was to investigate new therapeutic options to attenuate acute rejection in a rat lung allograft model. Cell-based gene therapies have recently been reported as a novel curative option in acute and chronic diseases for which conventional treatments are not available. We studied the effect of human interleukin 10 (hIL-10) on expressing bone marrow-derived mesenchymal stem cells (BMSCs) in combination with cyclosporine A (CsA) on acute rejection of lung allografts in the rat.
METHODS
Lung allotransplantation was performed from male Brown Norway donor to male Fisher (F344) rats. Rat BMSCs were transfected with hIL-10 in vitro and introduced in the graft prior to implantation. Group A (n = 5) received CsA intraperitoneally (2.5 mg/kg body weight) for 5 days post-transplant; Group B (n = 5) received BMSC and CsA and Group C (n = 5) received hIL-10-BMSC before implantation and CsA. Graft function was assessed by blood gas levels only from the graft on day 5; tissue was sampled for histological grading of rejection and measurement of the wet-to-dry ratio.
RESULTS
All Group A control animals showed severe signs of rejection. On Day 5, all grafts in Group C showed improved gas exchange (mean arterial partial pressure of oxygen 222.2 ± 40.38 mmHg vs 92.36 ± 20.92 mmHg in Group B and 42.72 ± 18.07 mmHg in Group A). Histological examination revealed moderate-to-severe rejection in all animals in Group A [International Society for Heart and Lung Transplantation Level III B (ISHLT)] in contrast to low-to-moderate rejection in Group B (II-IIIA) and much improved histological grade in Group C (I-IIA). Moreover, the wet-to-dry ratio was also reduced in Group C (4.8 ± 1.19 compared with 4.78 ± 0.62 in Group B and 9.36 ± 0.90 in Group A).
CONCLUSIONS
The hIL-10 BMSC represent a promising novel method for localized cell-based gene therapy for acute rejection in a rat lung allograft model.
目的
本研究旨在探讨一种新的治疗方法，以减轻大鼠肺移植模型中的急性排斥反应。细胞基因治疗最近被报道为一种新的治疗方法，可用于治疗传统治疗方法无效的急性和慢性疾病。我们研究了人白细胞介素 10（hIL-10）联合环孢素 A（CsA）对表达骨髓间充质干细胞（BMSCs）的大鼠肺同种异体移植物急性排斥反应的影响。
方法
将雄性布朗-挪威供体的肺移植到雄性 Fisher（F344）大鼠体内。体外转染大鼠 BMSCs 表达 hIL-10，移植前将其引入移植物。A 组（n=5）术后腹腔内给予 CsA（2.5mg/kg 体重）5 天；B 组（n=5）接受 BMSC 和 CsA；C 组（n=5）在移植前给予 hIL-10-BMSC 和 CsA。仅通过移植物在第 5 天评估移植物的血气水平；取样组织进行排斥反应的组织学分级和湿重-干重比的测量。
结果
所有 A 组对照动物均表现出严重的排斥反应迹象。第 5 天，C 组所有移植物的气体交换均得到改善（平均动脉部分氧分压 222.2±40.38mmHg 与 B 组 92.36±20.92mmHg 和 A 组 42.72±18.07mmHg）。组织学检查显示，A 组所有动物均出现中重度排斥反应[国际心肺移植学会（ISHLT）III B 级]，而 B 组为低-中度排斥反应（II-IIIA），C 组的组织学分级明显改善（I-IIA）。此外，C 组的湿重-干重比也降低（4.8±1.19 与 B 组 4.78±0.62 和 A 组 9.36±0.90）。
结论
hIL-10 BMSC 是一种有前途的新型方法，可用于大鼠肺移植模型中的急性排斥反应的局部细胞基因治疗。
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