Apoptotic bone marrow-derived mononuclear cells accelerate liver regeneration after extended resection

N. A. Onishchenko, A. Nikolskaya, Z. Z. Gonikova, L. A. Kirsanova, M. Shagidulin, V. Sevastianov
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Abstract

Objective: to compare the efficiency of regenerative processes in the liver using apoptotic bone marrow-derived mononuclear cells (BMMCs) and intact BMMCs from healthy animals on an extended liver resection (ELR) model.Materials and methods. Male Wistar rats (n = 77) with an ELR model (70–75%) were divided into 3 groups: group 1 (control with a single intraperitoneal injection of saline), group 2 (single intraperitoneal injection of unsorted intact BMMCs at a dose of 30–35 × 106, and group 3 (single intraperitoneal injection of apoptotic BMMCs at the same dose). Restoration of biochemical parameters of liver function and mass, as well as the emerging microstructural changes in hepatocytes in histological preparations, were monitored by assessing hepatocyte mitotic activity (MA) during the first 7–10 days after ELR.Results. It was found that in groups 2 and 3, as compared with group 1, there was no death after ELR modeling, and that the biochemical parameters of liver function normalized more rapidly (at days 10–14). Hepatocyte MA in group 3 sharply increased as early as on day 1, and mitotic index (MI) averaged 14‰, reaching 20.9‰ in some experiments; MI in the control group remained at the baseline by this time, while in group 2, MI was only 3.2‰. In group 3, liver mass recovered more rapidly after ELR to baseline values already at days 8–10, whereas the recovery was at day 12–14 and day 17–20 in group 2 and group 1, respectively. It was suggested that the more pronounced increase in the efficiency of regenerative processes in the liver after ELR in group 3 after using apoptotic BMMCs was due to the release from these cells of a large spectrum of formed paracrine factors, including various classes of RNA molecules involved in the regeneration process.Conclusion. Apoptotic BMMNCs have a more effective adaptive and regulatory potential than intact BMMCs because reorganizations are rapidly formed in the damaged liver cells, providing an early and more powerful activation of the targeted regenerative program.
凋亡的骨髓来源的单核细胞促进肝切除后的肝再生
目的:在延长肝切除(ELR)模型上,比较健康动物骨髓源性单核细胞(BMMCs)和凋亡的骨髓源性单核细胞(BMMCs)在肝脏再生过程中的效率。材料和方法。建立ELR模型的雄性Wistar大鼠(n = 77)(70-75%)分为3组:1组(对照组,单次腹腔注射生理盐水),2组(单次腹腔注射未分选的完整bmmc,剂量为30-35 × 106), 3组(单次腹腔注射相同剂量的凋亡bmmc)。通过评估肝细胞有丝分裂活性(MA),在elr后的前7-10天监测肝脏功能和质量的生化参数恢复以及组织学制剂中肝细胞出现的微结构变化。结果发现,与第1组相比,第2、3组大鼠在ELR造模后均无死亡,且肝功能生化指标恢复较快(第10-14天)。3组早在第1天肝细胞MA急剧升高,有丝分裂指数(MI)平均为14‰,部分实验达到20.9‰;此时,对照组的心肌梗死维持在基线水平,而第二组的心肌梗死仅为3.2‰。在第3组中,肝脏重量在ELR后8-10天恢复到基线值的速度更快,而第2组和第1组分别在第12-14天和第17-20天恢复。我们认为,使用凋亡的bmmc后,第3组ELR后肝脏再生过程效率的显著提高是由于这些细胞释放了大量形成的旁分泌因子,包括参与再生过程的各种RNA分子。凋亡的bmmnc比完整的bmmnc具有更有效的适应性和调节潜力,因为在受损的肝细胞中重组迅速形成,提供了早期和更强大的靶向再生程序激活。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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