Tracking and Therapeutic Value of Human Adipose Tissue–derived Mesenchymal Stem Cell Transplantation in Reducing Venous Neointimal Hyperplasia Associated with Arteriovenous Fistula

Yang, Binxia; Brahmbhatt, Akshaar; Torres, Evelyn Nieves; Thielen, Brian V.; McCall, Deborah; Engel, Sean; Bansal, Aditya; Pandey, Mukesh K.; Dietz, Allan B.; Leof, Edward B.; DeGrado, Timothy R.; Mukhopadhyay, Debabrata; Misra, Sanjay

doi:10.1148/radiol.2015150947

Cited by 35 publications

(36 citation statements)

References 51 publications

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“…In arterial injury, the presence of local stem cells and circulating stem cells contributing to the pathologic process is very well recognized but the role of these cells in VNH is less well recognized [22, 23]. Finally, a recent study demonstrated that adventitial delivery of human adipose derived mesenchymal stem cells to the outflow vein of murine AVF reduces VNH mediated by a reduction in gene expression of Mcp-1 [24]. …”

Section: Discussionmentioning

confidence: 99%

The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

Janardhanan¹,

Yang²,

Kilari³

et al. 2016

Journal of Vascular and Interventional Radiology

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Purpose Previous study has demonstrated that adventitial delivery of lentivirus mediated Vegf-A shRNA (LV-shRNA-Vegf-A, small hairpin RNA that inhibits Vegf-A gene expression) at the time of arteriovenous fistula (AVF) creation increases the lumen vessel area (LVA) of the outflow vein and reduces venous neointimal hyperplasia (VNH). However, the effect of decreasing Vegf-A and improving LVA decreases by 2-weeks as stenosis develops. The aim of the present study was to determine if a second dose of LV-shRNA-Vegf-A could improve LVA and decrease VNH. Methods Chronic kidney disease was created in C57BL/6 mice and 28 days later, a AVF was created by connecting right carotid artery to ipsilateral jugular vein. 5×106 plaque forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein immediately after AVF creation and a second dose of the same treatment fourteen days later. Animals were sacrificed at 21, 28, and 42 days after AVF creation for reverse transcription polymerase chain reaction (RT-PCR) and histomorphometric analyses. Results By day 21, there was a 25% increase in the average LVA (day 21: P=0.11), with a decrease in cell proliferation (day 21: P=0.0079, day 28: P=0.28; day 42: P=0.5), decrease in α-smooth muscle cell actin staining (day 21: P<0.0001, day 28: P<0.05; day 42: P=0.59), and decrease in hypoxic stress (day 21: P<0.001, day 28: P=0.28; day 42: P=0.46) in LV versus control shRNA vessels, respectively. Conclusion A second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21.

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Section: Discussionmentioning

confidence: 99%

The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

Janardhanan¹,

Yang²,

Kilari³

et al. 2016

Journal of Vascular and Interventional Radiology

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“…These data show that the entire vessel wall is involved in the processes that lead to access failure, and suggest additional targets for potential therapy; recent studies have demonstrated the potential to target and treat the adventitial space to prevent the adventitial response to injury and prevent AVF failure [56, 144, 145]. …”

Section: Mechanisms Contributing To Avf Maturation and Failurementioning

confidence: 99%

Future research directions to improve fistula maturation and reduce access failure

Patel

Hänisch

et al. 2016

Seminars in Vascular Surgery

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With the increasing prevalence of end stage renal disease there is a growing need for hemodialysis. Arteriovenous fistulae (AVF) are the preferred type of vascular access for hemodialysis but maturation and failure continue to present significant barriers to successful fistula use. AVF maturation integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes, in the setting of uremia, systemic inflammation, oxidative stress and preexistent vascular pathology. AVF can fail due to both failure to mature adequately to support hemodialysis, as well as development of neointimal hyperplasia (NIH) that narrows the AVF lumen, typically near the fistula anastomosis. Failure due to NIH involves vascular cell activation and migration and extracellular matrix remodeling with complex interactions of growth factors, adhesion molecules, inflammatory mediators, and chemokines, all of which result in maladaptive remodeling. Different strategies have been proposed to prevent and treat AVF failure, based on current understanding of the modes and pathology of access failure; these approaches range from appropriate patient selection and use of alternative surgical strategies for fistula creation, to the use of novel interventional techniques or drugs to treat failing fistulae. Effective treatments to prevent or treat AVF failure requires a multidisciplinary approach involving nephrologists, vascular surgeons and interventional radiologists, allowing careful patient selection and the use of tailored systemic or localized interventions to improve patient-specific outcomes. This review provides contemporary information on the underlying mechanisms of AVF maturation and failure and discusses the broad spectrum of options that can be tailored for specific therapy.

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“…An ongoing phase III randomized controlled trial is assessing the safety, efficacy, and patency outcomes of a perivascular sirolimus-eluting implant placed at the AVF anastomosis in hemodialysis patients receiving new AVFs (NCT02513303). Through the use of a similar concept, adipose-derived mesenchymal stem cells have been shown experimentally to reduce venous stenosis formation, and this technology is being proposed for use in a clinical trial (74). Finally, a small pilot study using adventitial delivery of calcitriol, a 1,25-dihydroxyvitamin D3 and inhibitor of Iex-1, at the time of angioplasty showed reduction in venous stenosis formation (75).…”

Section: Potential Future Molecular Targets That May Translate Into Tmentioning

confidence: 99%

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

Lee

Misra

2016

CJASN

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Vascular access dysfunction remains a major cause of morbidity and mortality in hemodialysis patients. At present there are few effective therapies for this clinical problem. The poor understanding of the pathobiology that leads to arteriovenous fistula (AVF) and graft (AVG) dysfunction remains a critical barrier to development of novel and effective therapies. However, in recent years we have made substantial progress in our understanding of the mechanisms of vascular access dysfunction. This article presents recent advances and new insights into the pathobiology of AVF and AVG dysfunction and highlights potential therapeutic targets to improve vascular access outcomes.

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Tracking and Therapeutic Value of Human Adipose Tissue–derived Mesenchymal Stem Cell Transplantation in Reducing Venous Neointimal Hyperplasia Associated with Arteriovenous Fistula

Cited by 35 publications

References 51 publications

The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

Future research directions to improve fistula maturation and reduce access failure

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

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