Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota.
J Am Soc Nephrol. 2020 Aug;31(8):1781-1795. doi: 10.1681/ASN.2019101042. Epub 2020 Jun 25.
Percutaneous transluminal angioplasty (PTA) is the first line of treatment for stenosis in the arteriovenous fistula (AVF) created to provide access for hemodialysis, but resenosis still occurs. Transplants of adipose-derived mesenchymal stem cells (AMSCs) labeled with green fluorescent protein (GFP) to the adventitia could reduce pro-inflammatory gene expression, possibly restoring patency in a murine model of PTA for venous stenosis.
Partial nephrectomy of male C57BL/6J mice induced CKD. Placement of the AVF was 28 days later and, 14 days after that, PTA of the stenotic outflow vein was performed with delivery of either vehicle control or AMSCs (5×10) to the adventitia of the vein. Mice were euthanized 3 days later and gene expression for interleukin-1 beta (IL-1) and tumor necrosis factor-alpha TNF-) analyzed, and histopathologic analysis performed on day 14 and 28. GFP (+) AMSCs were tracked after transplantation for up to 28 days and Doppler ultrasound performed weekly after AVF creation.
Gene and protein expression of IL-1 and TNF- fibrosis, proliferation, apoptosis and smooth muscle actin decreased, and the proportions of macrophage types (M2/M1) shifted in a manner consistent with less inflammation in AMSC-transplanted vessels compared to controls. After PTA, AMSC-treated vessels had significantly higher wall shear stress, average peak, and mean velocity, with increased lumen vessel area and decreased neointima/media area ratio compared to the control group. At 28 days after delivery, GFP (+) AMSC were present in the adventitia of the outflow vein.
AMSC-treated vessels had improved vascular remodeling with decreased proinflammatory gene expression, inflammation, and fibrotic staining compared to untreated vessels.
经皮腔内血管成形术（PTA）是治疗动静脉瘘（AVF）狭窄以提供血液透析通路的一线治疗方法，但再狭窄仍然存在。将绿色荧光蛋白（GFP）标记的脂肪来源间充质干细胞（AMSCs）移植到血管外膜可以减少促炎基因的表达，可能恢复 PTA 治疗静脉狭窄的小鼠模型中的通畅性。
雄性 C57BL/6J 小鼠行部分肾切除术诱导 CKD。28 天后放置 AVF，然后在狭窄的流出静脉 PTA 后 14 天，将载体对照或 AMSCs（5×10）输送到静脉外膜。3 天后处死小鼠，分析白细胞介素 1β（IL-1）和肿瘤坏死因子-α（TNF-）的基因表达，并在第 14 天和第 28 天进行组织病理学分析。移植后最多 28 天追踪 GFP（+）AMSCs，并在 AVF 形成后每周进行多普勒超声检查。
与对照组相比，IL-1 和 TNF-纤维化、增殖、凋亡和平滑肌肌动蛋白的基因和蛋白表达降低，巨噬细胞类型（M2/M1）的比例发生变化，提示炎症减轻。与对照组相比，PTA 后，AMSC 治疗的血管壁剪切力、平均峰值和平均速度明显更高，管腔血管面积增加，新生内膜/中膜面积比降低。在输送后 28 天，GFP（+）AMSC 存在于流出静脉的外膜中。
与未治疗的血管相比，AMSC 治疗的血管具有改善的血管重塑，促炎基因表达、炎症和纤维化染色减少。
