Prevention of neointimal hyperplasia induced by an endovascular stent via intravenous infusion of mesenchymal stem cells

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  • 1 Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, and
  • | 2 Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido;
  • | 3 NIPRO Life Science Site, NIPRO Corporation, Kusatsu, Shiga, Japan;
  • | 4 Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and
  • | 5 Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut
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OBJECTIVE

In-stent restenosis after percutaneous transluminal angioplasty and stenting (PTAS) due to neointimal hyperplasia is a potential cause of clinical complications, including repeated revascularization and ischemic events. Neointimal hyperplasia induced by an inflammatory response to the stent strut may be a possible mechanism of in-stent restenosis. Intravenous infusion of bone marrow–derived mesenchymal stem cells (MSCs) has been reported to show therapeutic efficacy for cerebral stroke, presumably by an antiinflammatory effect. This study aimed to determine whether MSCs can reduce or prevent neointimal hyperplasia induced by an endovascular stent.

METHODS

In this study, two types of bare metal stents were deployed using a porcine (mini-pig) model. One stent was implanted in the common carotid artery (CCA), which is considered quite similar to the human CCA, and the other was inserted in the superficial cervical artery (SCA), which is similar in size to the human middle cerebral artery. Angiographic images, intravascular ultrasound (IVUS) imaging, and microscopic images were used for analysis.

RESULTS

Angiographic images and IVUS studies revealed that intravenous infusion of MSCs immediately after deployment of stents prevented in-stent stenosis of the CCA and SCA. Histological analysis also confirmed that inflammatory responses around the stent struts were reduced in both the stented CCA and SCA in the mini-pig.

CONCLUSIONS

Intravenous infusion of MSCs inhibited the inflammatory reaction to an implanted stent strut, and prevented progressive neointimal hyperplasia in the stented CCA and SCA in a porcine model. Thus, MSC treatment could attenuate the recurrence of cerebral ischemic events after stenting.

ABBREVIATIONS

BT = body temperature; CAS = carotid artery stenting; CCA = common carotid artery; dBP = diastolic arterial blood pressure; DES = drug-eluting stent; DMEM = Dulbecco’s modified Eagle’s medium; DSA = digital subtraction angiography; FITC = fluorescein isothiocyanate; HR = heart rate; IgG1 = immunoglobulin G1; IL-1 = interleukin-1; IVUS = intravascular ultrasound; MCA = middle cerebral artery; MMP-9 = matrix metalloproteinase–9; MSC = mesenchymal stem cell; PTAS = percutaneous transluminal angioplasty and stenting; SaO2 = oxygen saturation; sBP = systolic arterial blood pressure; SCA = superficial cervical artery; TGF = transforming growth factor; TNF-α = tumor necrosis factor–α; TSG-6 = TNF-α–stimulated gene/protein 6.

The Neurosurgery Research & Education Foundation (NREF) is celebrating its 40th anniversary this month. Since its inception, the NREF has invested nearly $30 million in the future of neurosurgery through its support of basic science and clinical research, as well as life-long education, to foster improved outcomes for our patients with neurosurgical diseases. See the article by Agarwal et al. (pp 1905–1912).

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