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Basic Research
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Therapeutic Effect of Adipose Derived Mesenchymal Stem Cell Transplantation in Reducing Restenosis in a Murine Angioplasty Model

Chuanqi Cai, Sreenivasulu Kilari, Chenglei Zhao, Michael L. Simeon, Avanish Misra, Yiqing Li, Andre J. van Wijnen, Debabrata Mukhopadhyay and Sanjay Misra
JASN August 2020, 31 (8) 1781-1795; DOI: https://doi.org/10.1681/ASN.2019101042
Chuanqi Cai
1Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota
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Sreenivasulu Kilari
2Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota
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  • ORCID record for Sreenivasulu Kilari
Chenglei Zhao
2Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota
3Department of Vascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
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Michael L. Simeon
2Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota
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Avanish Misra
2Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota
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Yiqing Li
1Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Andre J. van Wijnen
4Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota
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Debabrata Mukhopadhyay
6Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, Florida
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Sanjay Misra
2Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota
5Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota
7Department of Radiology, Vascular and Interventional Radiology, Mayo Clinic, Rochester, Minnesota
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Significance Statement

The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, but several studies have shown that the primary patency rate at 1 year is approximately 60%. Percutaneous transluminal angioplasty (PTA) is the first line of treatment for AVF stenosis. However, the rate of restenosis after angioplasty is high and the primary patency rate after PTA treatment in AVFs at 6, 12, and 24 months is 61%, 42%, and 35%, respectively. Currently, no durable therapies prolong patency after angioplasty. This paper describes the use of adipose-derived mesenchymal stem cells to reduce stenosis after PTA treatment in a murine AVF model and provides rationale for potential clinical use.

Abstract

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 (5×105) to the adventitia of the vein. Mice were euthanized 3 days later and gene expression for interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha TNF-α) 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.

Results Gene and protein expression of IL-1β and TNF-α, 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.

Conclusions AMSC-treated vessels had improved vascular remodeling with decreased proinflammatory gene expression, inflammation, and fibrotic staining compared to untreated vessels.

  • arteriovenous fistula
  • stem cell
  • vascular access
  • Copyright © 2020 by the American Society of Nephrology
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Journal of the American Society of Nephrology: 31 (8)
Journal of the American Society of Nephrology
Vol. 31, Issue 8
August 2020
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Therapeutic Effect of Adipose Derived Mesenchymal Stem Cell Transplantation in Reducing Restenosis in a Murine Angioplasty Model
Chuanqi Cai, Sreenivasulu Kilari, Chenglei Zhao, Michael L. Simeon, Avanish Misra, Yiqing Li, Andre J. van Wijnen, Debabrata Mukhopadhyay, Sanjay Misra
JASN Aug 2020, 31 (8) 1781-1795; DOI: 10.1681/ASN.2019101042

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Therapeutic Effect of Adipose Derived Mesenchymal Stem Cell Transplantation in Reducing Restenosis in a Murine Angioplasty Model
Chuanqi Cai, Sreenivasulu Kilari, Chenglei Zhao, Michael L. Simeon, Avanish Misra, Yiqing Li, Andre J. van Wijnen, Debabrata Mukhopadhyay, Sanjay Misra
JASN Aug 2020, 31 (8) 1781-1795; DOI: 10.1681/ASN.2019101042
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