Intra-arterial injection of mesenchymal stem cells to accelerate neointima formation after endovascular stenting in a rabbit model

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  • 1 Biomedical Engineering,
  • | 2 Department of Clinical Neurosciences,
  • | 3 Hotchkiss Brain Institute,
  • | 4 Department of Radiology,
  • | 5 Department of Chemical and Petroleum Engineering, Schulich School of Engineering, and
  • | 6 Department of Cardiac Sciences, University of Calgary, Alberta, Canada
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OBJECTIVE

Delayed neointima formation over a neurovascular stent is associated with thrombotic complications that can lead to stroke. The purpose of this study was to evaluate whether an intra-arterial injection of mesenchymal stem cells (MSCs) after stent placement leads to improved neointima and reduced thrombus formation over the device.

METHODS

Solitaire stents were placed into the aortas of rabbits that were divided into MSC and control groups. The MSC group received an intra-arterial injection of MSCs through the same microcatheter used for stent deployment. Optical coherence tomography (OCT) was used to evaluate and compare neointima and thrombus formation in a blinded fashion. Explanted specimens were also imaged with scanning electron microscopy (SEM) and evaluated by observers blinded to group allocation using an endothelialization scoring system.

RESULTS

The 3-day MSC group was similar to the 7-day controls in terms of stent strut coverage ratio and maximum neointimal thickness, but these values were significantly higher than the 3-day control group based on a hierarchical mixed-effects linear regression analysis. SEM revealed a significantly higher endothelialization score for the MSC group compared with controls at the same time point. There was no difference in thrombus formation between any of the groups.

CONCLUSIONS

The intra-arterial injection of MSCs after endovascular stenting accelerated early neointima formation but had no effect on thrombus formation in this study. Larger studies are required to verify these findings and determine the durability and mechanism of this effect.

ABBREVIATIONS

ASA = acetylsalicylic acid; CI = confidence interval; DSA = digital subtraction angiography; MSC = mesenchymal stem cell; OCT = optical coherence tomography; SEM = scanning electron microscopy.

Schematics of transseptal interforniceal resection of a superiorly recessed colloid cyst. ©Mark Souweidane, published with permission. See the article by Tosi et al. (pp 813–819).

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  • 1

    Van Belle E, Tio FO, Couffinhal T, Maillard L, Passeri J, Isner JM. Stent endothelialization. Time course, impact of local catheter delivery, feasibility of recombinant protein administration, and response to cytokine expedition. Circulation. 1997;95(2):438448.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Van Belle E, Tio FO, Chen D, et al. Passivation of metallic stents after arterial gene transfer of phVEGF165 inhibits thrombus formation and intimal thickening. J Am Coll Cardiol. 1997;29(6):13711379.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Finn AV, Joner M, Nakazawa G, et al. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation. 2007;115(18):24352441.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Riedel CH, Tietke M, Alfke K, Stingele R, Jansen O. Subacute stent thrombosis in intracranial stenting. Stroke. 2009;40(4):13101314.

  • 5

    Lessne ML, Shah P, Alexander MJ, et al. Thromboembolic complications after Neuroform stent-assisted treatment of cerebral aneurysms: the Duke Cerebrovascular Center experience in 235 patients with 274 stents. Neurosurgery. 2011;69(2):369375.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Brasiliense LBC, Stanley MA, Grewal SS, et al. Silent ischemic events after Pipeline embolization device: a prospective evaluation with MR diffusion-weighted imaging. J Neurointerv Surg. 2016;8(11):11361139.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Matsuda Y, Chung J, Lopes DK. Analysis of neointima development in flow diverters using optical coherence tomography imaging. J Neurointerv Surg. 2018;10(2):162167.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Matsuda Y, Jang DK, Chung J, Wainwright JM, Lopes D. Preliminary outcomes of single antiplatelet therapy for surface-modified flow diverters in an animal model: analysis of neointimal development and thrombus formation using OCT. J Neurointerv Surg. 2019;11(1):7479.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Lenz-Habijan T, Bhogal P, Bannewitz C, et al. Prospective study to assess the tissue response to HPC-coated p48 flow diverter stents compared to uncoated devices in the rabbit carotid artery model. Eur Radiol Exp. 2019;3(1):47.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Bhogal P, Lenz-Habijan T, Bannewitz C, et al. The pCONUS HPC: 30-day and 180-day in vivo biocompatibility results. Cardiovasc Intervent Radiol. 2019;42(7):10081015.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Martínez Moreno R, Bhogal P, Lenz-Habijan T, et al. In vivo canine study of three different coatings applied to p64 flow-diverter stents: initial biocompatibility study. Eur Radiol Exp. 2019;3(1):3.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Meng X, Chen M, Su W, et al. The differentiation of mesenchymal stem cells to vascular cells regulated by the HMGB1/RAGE axis: its application in cell therapy for transplant arteriosclerosis. Stem Cell Res Ther. 2018;9(1):85.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Zhang L, Issa Bhaloo S, Chen T, Zhou B, Xu Q. Role of resident stem cells in vessel formation and arteriosclerosis. Circ Res. 2018;122(11):16081624.

  • 14

    Xu J, Wu D, Yang Y, Ji K, Gao P. Endotheliallike cells differentiated from mesenchymal stem cells attenuate neointimal hyperplasia after vascular injury. Mol Med Rep. 2016;14(5):48304836.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Adibi A, Eesa M, Wong JH, Sen A, Mitha AP. Combined endovascular coiling and intra-aneurysmal allogeneic mesenchymal stromal cell therapy for intracranial aneurysms in a rabbit model: a proof-of-concept study. J Neurointerv Surg. 2017;9(7):707712.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Avery MB, Belanger BL, Bromley A, Sen A, Mitha AP. Mesenchymal stem cells exhibit both a proinflammatory and anti-inflammatory effect on saccular aneurysm formation in a rabbit model. Stem Cells Int. 2019;2019:3618217.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Sultan S, Kavanagh EP, Bonneau M, Kang C, Alves A, Hynes NM. Kinetics of endothelialization of the multilayer flow modulator and single-layer arterial stents. Vascular. 2016;24(1):7887.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Houston SA, Ugusman A, Gnanadesikan S, Kennedy S. An investigation of the antiplatelet effects of succinobucol (AGI-1067). Platelets. 2017;28(3):295300.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Tao H, Han Z, Han ZC, Li Z. Proangiogenic features of mesenchymal stem cells and Their therapeutic applications. Stem Cells Int. 2016;2016:1314709.

  • 20

    Li M, Li S, Yu L, et al. Bone mesenchymal stem cells contributed to the neointimal formation after arterial injury. PLoS One. 2013;8(12):e82743.

  • 21

    Rouchaud A, Brinjikji W, Dai D, et al. Autologous adipose-derived mesenchymal stem cells improve healing of coiled experimental saccular aneurysms: an angiographic and histopathological study. J Neurointerv Surg. 2018;10(1):6065.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Hwang CW, Johnston PV, Gerstenblith G, et al. Stem cell impregnated nanofiber stent sleeve for on-stent production and intravascular delivery of paracrine factors. Biomaterials. 2015;52:318326.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Wu X, Wang G, Tang C, et al. Mesenchymal stem cell seeding promotes reendothelialization of the endovascular stent. J Biomed Mater Res A. 2011;98(3):442449.

  • 24

    Nakazaki M, Oka S, Sasaki M, et al. Prevention of neointimal hyperplasia induced by an endovascular stent via intravenous infusion of mesenchymal stem cells. J Neurosurg. 2020;133(6):17731785.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Liu Z, Wu C, Zou X, et al. Exosomes derived from mesenchymal stem cells inhibit neointimal hyperplasia by activating the Erk1/2 signalling pathway in rats. Stem Cell Res Ther. 2020;11(1):220.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Chang HK, Kim PH, Kim DW, et al. Coronary stents with inducible VEGF/HGF-secreting UCB-MSCs reduced restenosis and increased re-endothelialization in a swine model. Exp Mol Med. 2018;50(9):114.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Ughi GJ, Van Dyck CJ, Adriaenssens T, et al. Automatic assessment of stent neointimal coverage by intravascular optical coherence tomography. Eur Heart J Cardiovasc Imaging. 2014;15(2):195200.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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