Mesenchymal Stem Cells Loaded with Gelatin Microcryogels Attenuate Renal Fibrosis
Mesenchymal Stem Cells Loaded with Gelatin Microcryogels Attenuate Renal Fibrosis
复制标题
装载明胶微冷冻凝胶的间充质干细胞可减轻肾纤维化
DOI：
10.1155/2019/6749326
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发表时间：
2019-10-31
影响因子：
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通讯作者：
Wu, Di
中科院分区：
文献类型：
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作者：
Geng, Xiaodong;Hong, Quan;Wu, Di
背景利用间充质干细胞（MSC）通过不同方法治疗慢性肾脏疾病（CKD）已取得长足进步。在这项研究中，我们的目的是探讨明胶微冻凝胶（GM）作为细胞治疗载体，以阻止CKD的进展的潜在机制。方法.在体实验中，将带蒂大网膜瓣与MSC负载的GMs一起包裹在5/6的大鼠肾切除后的肾脏上。评价治疗效果。在体外，将TNF-α、TGF-β和MSC添加到HK-2细胞培养系统的培养基中，并通过qPCR评估参与抗炎和抗纤维化作用的关键基因。结果MSC移植12周后，肾功能，如血清肌酐，尿素氮和24小时尿蛋白，显着改善。取5/6肾切除的大鼠肾组织，用带蒂网膜瓣包裹载MSC的GMs，免疫组化染色和Western blot分析Ⅳ型胶原、α-SMA和TGF-β的表达。MSC负载的GMs还通过诱导HO-1、BMP-7和HGF的上调以及MCP-1的下调在mRNA水平上显示抗纤维化作用。负载MSC的GM治疗四个星期后，我们发现TNF-α和IL-6的mRNA水平明显降低。MSC-条件培养基（MSC-CM）显示TNF-α诱导的HK-2细胞IL-8和IL-6 mRNA表达逆转，E-cadherin mRNA表达上调，TGF-β诱导的HK-2细胞IV型胶原、α-SMA和纤维连接蛋白（FN）mRNA表达降低。结论.我们通过观察带蒂大网膜瓣膜填充MSC负载的GMs的抗炎和抗纤维化作用，证明了带蒂大网膜瓣膜对5/6肾切除的肾脏具有保护作用。
Background. The treatment of chronic kidney diseases (CKDs) by different approaches using mesenchymal stem cells (MSCs) has made great strides. In this study, we aimed to explore the potential mechanism of gelatin microcryogels (GMs) as a cell therapeutic vector to block the progression of CKD. Methods. In vivo, the pedicled omentum valve with MSC-loaded GMs was packed onto 5/6 nephrectomized kidneys derived from rats. The therapeutic effects were evaluated. In vitro, TNF-alpha, TGF-beta, and MSCs were added to the medium of the HK-2 cell culture system, and key genes involved in anti-inflammatory and antifibrosis effects were evaluated by qPCR. Results. After 12 weeks of MSC transplantation, kidney functions, such as serum creatinine, urea nitrogen, and 24-hour urine protein, were significantly improved. The pedicled omentum valve was packed with MSC-loaded GMs onto the 5/6 nephrectomized kidney, and the expressions of collagen IV, alpha-SMA, and TGF-beta were all evaluated by immunohistochemical staining and western blot analysis. MSC-loaded-GMs also showed antifibrotic effects by inducing the upregulation of HO-1, BMP-7, and HGF and the downregulation of MCP-1 at the mRNA level. Four weeks after MSC-loaded GM treatment, we found that the mRNA levels of TNF-alpha and IL-6 were clearly reduced. MSC-conditional medium (MSC-CM) showed that the TNF-alpha-induced expression of IL-8 and IL-6 mRNA was reversed; E-cadherin mRNA was upregulated; and the TGF-beta-induced expression of collagen IV, alpha-SMA, and fibronectin (FN) mRNA in HK-2 cells was reduced. Conclusions. We demonstrated that the pedicled omentum valve packed with MSC-loaded GMs had a renal protective effect on the 5/6 nephrectomized kidney by observing the anti-inflammatory and antifibrosis effects.