TY - JOUR
T1 - Therapeutic effect of adipose derived mesenchymal stem cell transplantation in reducing restenosis in a murine angioplasty model
AU - Cai, Chuanqi
AU - Kilari, Sreenivasulu
AU - Zhao, Chenglei
AU - Simeon, Michael L.
AU - Misra, Avanish
AU - Li, Yiqing
AU - van Wijnen, Andre J.
AU - Mukhopadhyay, Debabrata
AU - Misra, Sanjay
N1 - Publisher Copyright:
Copyright © 2020 by the American Society of Nephrology
PY - 2020/8
Y1 - 2020/8
N2 - Background 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. Methods 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 (53105) to the adventitia of the vein. Mice were euthanized 3 days later and gene expression for interleukin-1 beta (IL-1b) and tumor necrosis factor-alpha TNF-a) analyzed, and histopathologic analysis performed on day 14 and 28. GFP (1) AMSCs were tracked after transplantation for up to 28 days and Doppler ultrasound performed weekly after AVF creation. Results Gene and protein expression of IL-1b and TNF-a, 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 (1) AMSC were present in the adventitia of the outflow vein. Conclusions AMSC-treated vessels had improved vascular remodeling with decreased proinflammatory gene expression, inflammation, and fibrotic staining compared to untreated vessels.
AB - Background 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. Methods 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 (53105) to the adventitia of the vein. Mice were euthanized 3 days later and gene expression for interleukin-1 beta (IL-1b) and tumor necrosis factor-alpha TNF-a) analyzed, and histopathologic analysis performed on day 14 and 28. GFP (1) AMSCs were tracked after transplantation for up to 28 days and Doppler ultrasound performed weekly after AVF creation. Results Gene and protein expression of IL-1b and TNF-a, 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 (1) AMSC were present in the adventitia of the outflow vein. Conclusions AMSC-treated vessels had improved vascular remodeling with decreased proinflammatory gene expression, inflammation, and fibrotic staining compared to untreated vessels.
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U2 - 10.1681/ASN.2019101042
DO - 10.1681/ASN.2019101042
M3 - Article
C2 - 32587073
AN - SCOPUS:85089128646
SN - 1046-6673
VL - 31
SP - 1781
EP - 1795
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 8
ER -