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间充质干细胞和富血小板血浆在胆管结扎诱导的肝硬化大鼠模型中的协同肝保护作用

Synergistic Hepatoprotective Effects of Mesenchymal Stem Cells and Platelet-Rich Plasma in a Rat Model of Bile Duct Ligation-Induced Liver Cirrhosis.

作者信息

Shivaramu Shivaraju, Maiti Swapan Kumar, Banu Shajahan Amitha, Kalaiselvan Elangovan, Sharun Khan, Mishra Mamta, Mohan Divya, Palakkara Sangeetha, Kumar Sunil, Sahoo Monalisa, Hescheler Jürgen

机构信息

Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India.

Graduate Institute of Medicine, Yuan Ze University, Taoyuan 32003, Taiwan.

出版信息

Cells. 2024 Feb 26;13(5):404. doi: 10.3390/cells13050404.

Abstract

Liver cirrhosis poses a global health challenge marked by significant prevalence and mortality. Current therapeutic options are limited by high costs and immune-mediated rejection, necessitating the exploration of innovative strategies to enhance hepatic self-rehabilitation, and counteract the underlying pathological mechanisms. We evaluated the hepatoprotective activity of rat adipose-derived mesenchymal stem cells (ADMSCs) in combination with platelet-rich plasma (PRP) and recombinant human hepatocyte growth factor (rh-HGF) on a rat model of liver fibrosis/cirrhosis induced by bile duct ligation (BDL). Treatment with PRP or rh-HGF alone did not yield significant hepatoprotection in the BDL-induced liver cirrhosis model. However, ADMSC transplantation alone exhibited the potential to alleviate impaired liver conditions. The combination of PRP and rh-HGF demonstrated superior ameliorative effects compared to either treatment alone. Notably, the combination of ADMSC + PRP or ADMSC + rh-HGF significantly enhanced hepatoprotective capacity compared to individual or combined PRP and rh-HGF therapies. Injection of ADMSC via the tail vein reduced inflammation, hepatocyte damage, and collagen deposition, improving overall liver function. This improvement was more pronounced when ADMSC was administered with PRP and rh-HGF versus monotherapy. Our study concludes that ADMSCs exert antifibrotic effects by inhibiting hepatic stellate cell proliferation, collagen synthesis, and inducing apoptosis. ADMSCs also demonstrate immune-modulatory effects and transdifferentiate into hepatic progenitor cells, secreting trophic factors, cytokines, and chemokines that promote impaired liver regeneration. The observed arrest in liver fibrosis progression highlights the potential therapeutic impact of these interventions.

摘要

肝硬化是一项全球性的健康挑战,具有较高的发病率和死亡率。目前的治疗选择受到高成本和免疫介导排斥反应的限制,因此有必要探索创新策略来增强肝脏自我修复能力,并对抗潜在的病理机制。我们评估了大鼠脂肪来源间充质干细胞(ADMSC)联合富血小板血浆(PRP)和重组人肝细胞生长因子(rh-HGF)对胆管结扎(BDL)诱导的大鼠肝纤维化/肝硬化模型的肝脏保护活性。在BDL诱导的肝硬化模型中,单独使用PRP或rh-HGF治疗并未产生显著的肝脏保护作用。然而,单独移植ADMSC显示出缓解肝脏受损状况的潜力。与单独治疗相比,PRP和rh-HGF联合使用表现出更优的改善效果。值得注意的是,与单独或联合使用PRP和rh-HGF治疗相比,ADMSC + PRP或ADMSC + rh-HGF联合使用显著增强了肝脏保护能力。通过尾静脉注射ADMSC可减轻炎症、肝细胞损伤和胶原沉积,改善整体肝功能。与单一疗法相比,ADMSC与PRP和rh-HGF联合使用时这种改善更为明显。我们的研究得出结论,ADMSC通过抑制肝星状细胞增殖、胶原合成并诱导凋亡发挥抗纤维化作用。ADMSC还表现出免疫调节作用,并可转分化为肝祖细胞,分泌促进受损肝脏再生的营养因子、细胞因子和趋化因子。观察到的肝纤维化进展停滞突出了这些干预措施的潜在治疗影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3651/10931218/3022e89ac9cf/cells-13-00404-g001.jpg

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