Division of Nephrology, John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois; Hektoen Institute of Medicine, Chicago, Illinois; and Division of Nephrology, Department of Medicine, University of Illinois Medical Center at Chicago, Illinois; and.
Hektoen Institute of Medicine, Chicago, Illinois; and.
J Am Soc Nephrol. 2014 Jun;25(6):1270-81. doi: 10.1681/ASN.2013040387. Epub 2014 Mar 13.
Stem cells show promise in the treatment of AKI but do not survive long term after injection. However, organ repair has been achieved by extending and attaching the omentum, a fatty tissue lying above the stomach containing stem cells, to various organs. To examine whether fusing the omentum to a subtotally nephrectomized kidney could slow the progression of CKD, we used two groups of rats: an experimental group undergoing 5/6 nephrectomy only and a control group undergoing 5/6 nephrectomy and complete omentectomy. Polydextran gel particles were administered intraperitoneally before suture only in the experimental group to facilitate the fusion of the omentum to the injured kidney. After 12 weeks, experimental rats exhibited omentum fused to the remnant kidney and had lower plasma creatinine and urea nitrogen levels; less glomerulosclerosis, tubulointerstitial injury, and extracellular matrix; and reduced thickening of basement membranes compared with controls. A fusion zone formed between the injured kidney and the omentum contained abundant stem cells expressing stem cell antigen-1, Wilms' tumor 1 (WT-1), and CD34, suggesting active, healing tissue. Furthermore, kidney extracts from experimental rats showed increases in expression levels of growth factors involved in renal repair, the number of proliferating cells, especially at the injured edge, the number of WT-1-positive cells in the glomeruli, and WT-1 gene expression. These results suggest that contact between the omentum and injured kidney slows the progression of CKD in the remnant organ, and this effect appears to be mediated by the presence of omental stem cells and their secretory products.
干细胞在 AKI 的治疗中显示出前景,但在注射后不能长期存活。然而,通过将位于胃上方的含有干细胞的脂肪组织网膜延伸并附着到各种器官上,已经实现了器官修复。为了研究将网膜融合到部分肾切除的肾脏中是否可以减缓 CKD 的进展,我们使用了两组大鼠:仅接受 5/6 肾切除术的实验组和接受 5/6 肾切除术和完全网膜切除术的对照组。只有实验组在缝合前腹膜内给予聚葡聚糖凝胶颗粒,以促进网膜与受损肾脏的融合。12 周后,实验组大鼠的网膜与残余肾脏融合,血浆肌酐和尿素氮水平较低;肾小球硬化、肾小管间质损伤和细胞外基质减少;与对照组相比,基底膜增厚减少。受伤肾脏和网膜之间形成融合区,富含表达干细胞抗原-1、Wilms 瘤 1(WT-1)和 CD34 的干细胞,表明存在活跃的愈合组织。此外,实验组大鼠的肾脏提取物中与肾脏修复相关的生长因子表达水平增加,增殖细胞数量增加,尤其是在受损边缘,肾小球中 WT-1 阳性细胞数量增加,WT-1 基因表达增加。这些结果表明,网膜与受损肾脏的接触可减缓残余器官中 CKD 的进展,这种作用似乎是由网膜干细胞及其分泌产物的存在介导的。