Mesenchymal Stem Cell Transplantation Attenuates Venous Stenosis of Hemodialysis Vascular Access Arteriovenous Fistula [Mouse GV_MSCvsNT]

Arteriovenous fistula (AVF) is the preferred vascular access for patients undergoing hemodialysis and the majority of AVFs fail because of venous intimal hyperplasia (VNH). Results from our lab have shown that adipose tissue-derived mesenchymal stem cell (MSC) transplantation to the adventitia of the outflow vein of AVF attenuates VNH in an immunodeficient mice. in the present study efficacy of AMSCs transplantation in treating AVF failure was tested in a chronic kidney disease (CKD) followed by an AVF created in C57BL/6 mice and porcine models as described in methods. Moreover, a phase 1 trial was performed in small group of endstage renal disease (ESRD) patients who are in hemodialysis. To explore the molecular mechanisms involved in MSCs transplantation improving AVF durability, we performed RNA-seq transcriptome analysis of the outflow veins of AVFs excised from mice and Pigs the after adventitial transplantation of MSCs from the donor inbred C57BL/6 mice or pigs respectively. RNA-seq on AMSCs isolated from donor mice, pigs and from patients of Phase 1 study was performed and CD markers of MSCs were compared to assess the homogenicity of isolated AMSCs with in the species.Mesenchymal Stem Cell Transplantation Attenuates Venous Stenosis of Hemodialysis Vascular Access Arteriovenous Fistula Overall design: Chronic Kidney disease created to a C57BL6J mouse as described in methods. 28days later an arteriovenous fistula was clreated by ligation of carotid artery and jugular vein. immidiatly after AVF creation, 250000 MSCs from C57 donor mouse of same gender were layred on the adventitia of the AVF outflow veins. 3 days after AVF creation, animals were euthanized and the outflow veins of AVFs were harvested.