Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
World J Gastroenterol. 2013 Mar 28;19(12):1984-91. doi: 10.3748/wjg.v19.i12.1984.
To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF).
Chinese experimental miniature swine were randomly divided into four groups (n = 7), and all animals were given D-galactosamine (D-gal) to induce ALF. Group A animals were then injected with 40 mL saline via the portal vein 24 h after D-gal induction; Group B animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h, 2 d and 4 d after D-gal induction; Group C received approximately 1 × 10(8) green fluorescence protein (GFP)-labeled MSCs (GFP-MSCs) suspended in 40 mL normal saline via the portal vein 24 h after D-gal induction; Group D animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h after D-gal induction, MSCs transplantation was then carried out at 24 h after D-gal induction, and finally 2 mg/kg IL-1Ra was injected via the ear vein 1 d and 3 d after surgery as before. Liver function, serum inflammatory parameters and pathological changes were measured and the fate of MSCs was determined.
The optimal efficiency of transfection (97%) was achieved at an multiplicity of infection of 80, as observed by fluorescence microscopy and flow cytometry (FCM). Over 90% of GFP-MSCs were identified as CD44+ CD90+ CD45- MSCs by FCM, which indicated that most GFP-MSCs retained MSCs characteristics. Biochemical assays, the levels of serum inflammatory parameters and histological results in Group D all showed a significant improvement in liver injury compared with the other groups (P < 0.05). The number of GFP-MSCs in Group D was also greater than that in Group B, and the long-term cell proliferation rate was also better in Group D than in the other groups.
MSCs transplantation is useful in ALF, IL-1Ra plays an important role in alleviating the inflammatory condition, and combination therapy with MSCs transplantation and IL-1Ra is a promising treatment for ALF.
研究骨髓间充质干细胞（MSCs）移植联合白细胞介素-1 受体拮抗剂（IL-1Ra）治疗急性肝衰竭（ALF）的疗效。
将中国实验小型猪随机分为 4 组（n=7），所有动物均给予 D-半乳糖胺（D-gal）诱导 ALF。D-gal 诱导后 24 h，A 组动物门静脉内注射 40 mL 生理盐水；B 组动物 D-gal 诱导后 18 h、2 d 和 4 d 经耳静脉内注射 2 mg/kg IL-1Ra；C 组接受约 1×10(8)个绿色荧光蛋白（GFP）标记的 MSCs（GFP-MSCs）悬浮于 40 mL 生理盐水中，D-gal 诱导后 24 h 门静脉内注射；D 组动物 D-gal 诱导后 18 h 经耳静脉内注射 2 mg/kg IL-1Ra，D-gal 诱导后 24 h 行 MSCs 移植，术后 1 d 和 3 d 分别再次经耳静脉内注射 2 mg/kg IL-1Ra，同前。检测肝功能、血清炎症参数和组织病理学变化，确定 MSCs 的命运。
荧光显微镜和流式细胞术（FCM）观察到，感染复数为 80 时转染效率最佳（97%）。FCM 鉴定超过 90%的 GFP-MSCs 为 CD44+ CD90+ CD45- MSCs，表明大多数 GFP-MSCs 保留了 MSCs 特征。与其他组相比，D 组的生化检测、血清炎症参数水平和组织学结果均显示肝损伤明显改善（P<0.05）。D 组 GFP-MSCs 数量也多于 B 组，D 组长期细胞增殖率也优于其他组。
MSCs 移植对 ALF 有效，IL-1Ra 对缓解炎症状态有重要作用，MSCs 移植联合 IL-1Ra 治疗 ALF 具有广阔前景。
