Sultan Agung Islamic University (UNISSULA), Semarang, Indonesia.
Universitas Sumatera Utara, Medan, Indonesia.
Folia Med (Plovdiv). 2020 Mar 31;62(1):52-58. doi: 10.3897/folmed..e47712.
Mesenchymal stem cells (MSCs) migrate and transmigrate to acute liver failure (ALF) area due to vascular endothelial growth factor (VEGF) stimulation as an attractant molecule then actively giving the paracrine signaling and or differentiating into primary hepatocytes, however the best route of MSCs transplanted to liver injury area remains unclear.
In this study we compare intravenous (IV) and intraperitoneal (IP) route of MSCs administration by analyzing serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin level as improvement markers of liver function and VEGF as attractant-proliferation molecule on days 2 and 5.
Eighteen male Sprague-Dawley rats weighting 200 g were used in this study. They were divided in three study groups: vehicle control, IP and IV groups. The IV group was treated by MSCs at dose 1×106 by lateral tail vein injection and IP group received 1×106 MSCs via IP injection. The level of SGPT, SGOT and bilirubin were measured by an automatic analyzer, the VEGF level using enzyme-linked immunosorbent assay (ELISA), while the CD73 expression was evaluated using immunohistochemistry.
This study showed that IV injection of MSCs was more efficient for increasing liver function than IP treatment group that confirmed by the observed significant decrease in SGPT, SGOT and bilirubin level on days 2 and 5 (p<0.001). This effect was most likely mediated by the significant increase of VEGF level (p<0.05) on days 2 and 5.
Our result conclude that an IV administration of MSCs was more efficacious than the IP administration for liver injury regeneration.
间充质干细胞(MSCs)在血管内皮生长因子(VEGF)的刺激下迁移并穿过血管内皮到达急性肝衰竭(ALF)区域,作为一种吸引分子,然后积极提供旁分泌信号或分化为原代肝细胞,但 MSCs 移植到肝损伤区域的最佳途径仍不清楚。
在这项研究中,我们通过分析血清谷氨酸丙酮酸转氨酶(SGPT)、血清谷氨酸草酰乙酸转氨酶(SGOT)和胆红素水平来比较静脉(IV)和腹腔(IP)途径给予 MSCs 作为肝功能改善标志物,以及 VEGF 作为吸引-增殖分子在第 2 天和第 5 天的作用。
本研究使用了 18 只雄性 Sprague-Dawley 大鼠,体重 200g。它们被分为三组:对照组、IP 组和 IV 组。IV 组通过侧尾静脉注射给予 1×106 MSCs,IP 组通过腹腔注射给予 1×106 MSCs。使用自动分析仪测量 SGPT、SGOT 和胆红素水平,使用酶联免疫吸附试验(ELISA)测量 VEGF 水平,使用免疫组织化学评估 CD73 表达。
本研究表明,与 IP 治疗组相比,IV 注射 MSCs 更能有效提高肝功能,这从第 2 天和第 5 天 SGPT、SGOT 和胆红素水平的显著下降(p<0.001)中得到证实。这种效果很可能是通过 VEGF 水平的显著增加(p<0.05)介导的。
我们的结果表明,IV 给予 MSCs 比 IP 给予 MSCs 更能有效地促进肝损伤再生。