Use of MR Cell Tracking to Evaluate Targeting of Glial Precursor Cells to Inflammatory Tissue by Exploiting the Very Late Antigen-4 Docking Receptor

Gorelik, Michael; Orukari, Inema; Wang, Joanne; Galpoththawela, Shashikala; Kim, Heechul; Lévy, Michaël; Gilad, Assaf A.; Bar‐Shir, Amnon; Kerr, Douglas A.; Levchenko, Andre; Bulte, Jeff W.M.; Walczak, Piotr

doi:10.1148/radiol.12112212

Cited by 46 publications

(50 citation statements)

References 35 publications

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“…One such technique is magnetic resonance imaging (MRI). 5,6 A catheter-based intraarterial injection technique is ideally suited for that purpose. We therefore explored, in a systematic fashion, the factors that determine the safety of intracarotid cell delivery using a microcatheter technique.…”

Section: Introductionmentioning

confidence: 99%

Cell Size and Velocity of Injection are Major Determinants of the Safety of Intracarotid Stem Cell Transplantation

Janowski

Lyczek

Engels

et al. 2013

J Cereb Blood Flow Metab

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127

101

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Intracarotid transplantation has shown potential for efficient stem cell delivery to the brain. However, reported complications, such as compromised cerebral blood flow (CBF), prompted us to perform further safety studies. Glial-restricted precursors (GRPs) and mesenchymal stem cells (MSCs) were transplanted into the internal carotid artery of rats (n ¼ 99), using a microcatheter. Magnetic resonance imaging was used to detect post-transplantation complications, including the development of stroke, for the following experimental variables: cell size, cell dose, cell infusion velocity, delay between artery occlusion and cell infusion, discordant versus concordant xenografting, and intracarotid transplantation with preserved versus compromised blood flow. Immunocompatibility and delayed infusion did not affect the number of complications. An infusion velocity over X1 mL/minute often resulted in stroke (27 out of 44 animals), even with an infusion of vehicle, whereas a lower velocity (0.2 mL/minute) was safe for the infusion of both vehicle and smaller cells (GRPs, diameter ¼ 15 mm). Infusion of larger cells (MSCs, diameter ¼ 25 mm) resulted in a profound decrease (75±17%) in CBF. Stroke lesions occurred frequently (12 out of 15 animals) when injecting 2 Â 10 6 MSCs, but not after lowering the dose to 1 Â 10 6 cells. The present results show that cell size and infusion velocity are critical factors in developing safe protocols for intracarotid stem cell transplantation. Journal of Cerebral Blood INTRODUCTIONThe intravascular route of stem cell delivery has met with increasing interest because of the minimally invasive nature of the procedure and the potential for broad cell distribution. Recent reports 1,2 have revealed positive effects of intravascular cell transplantation in animal models of neurologic disorders. The evaluation of neural cell distribution after intravenous cell transplantation has shown that most of the cells are initially entrapped within the lungs and do not travel to the brain.3 It has been hypothesized that an intraarterial approach would be a more efficient route of cell delivery to the brain, as this approach avoids the pulmonary circulation. This approach is particularly attractive when selecting and sorting cells for adhesion molecules, which can enhance cell homing and therapeutic outcome. 4 Moreover, it has been recently shown that transfection of adhesion molecules in progenitor cells results in a dramatic increase of their homing to inflamed brain endothelium.

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Section: Introductionmentioning

confidence: 99%

Cell Size and Velocity of Injection are Major Determinants of the Safety of Intracarotid Stem Cell Transplantation

Janowski

Lyczek

Engels

et al. 2013

J Cereb Blood Flow Metab

Self Cite

127

101

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“…129,130 Direct intramyocardial injection was shown to result in higher cell delivery efficiency to the infarcted myocardium, however, being a technically quite challenging technique to execute. 131 Another example of how in vivo cell tracking may help in defining the optimal delivery route was demonstrated in a study in rats by Gorelik et al 132 In this study, homing of glial precursor cell delivery to inflamed brain after intra-arterial injection was studied. To this end, the cells were labelled with iron oxide particles and injected into the carotid artery and their homing to the brain was monitored by MRI.…”

Section: Clinically Relevant Insights Gained From Pre-clinical Studiementioning

confidence: 86%

Nanoparticles and clinically applicable cell tracking

Bernsen

Guenoun

Tiel

et al. 2015

BJR

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In vivo cell tracking has emerged as a much sought after tool for design and monitoring of cell-based treatment strategies. Various techniques are available for pre-clinical animal studies, from which much has been learned and still can be learned. However, there is also a need for clinically translatable techniques. Central to in vivo cell imaging is labelling of cells with agents that can give rise to signals in vivo, that can be detected and measured non-invasively. The current imaging technology of choice for clinical translation is MRI in combination with labelling of cells with magnetic agents. The main challenge encountered during the cell labelling procedure is to efficiently incorporate the label into the cell, such that the labelled cells can be imaged at high sensitivity for prolonged periods of time, without the labelling process affecting the functionality of the cells. In this respect, nanoparticles offer attractive features since their structure and chemical properties can be modified to facilitate cellular incorporation and because they can carry a high payload of the relevant label into cells. While these technologies have already been applied in clinical trials and have increased the understanding of cell-based therapy mechanism, many challenges are still faced.

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“…157 Several researchers have investigated the role of integrin activation in improving cell adhesion, migration, and neurite outgrowth. [158][159][160][161][162][163] In addition, it has been shown that inhibitory factors can influence the activation state of integrins and decrease the ability of the cells to interact with their extracellular environment. 159,162,163 It is therefore possible to change the expression profile of integrins or their activation state to promote the adhesion of RPE cells to pathological Bruch's membrane prior to transplantation.…”

Section: Enhancing the Adhesion And Survival Of Transplanted Rpe Cellsmentioning

confidence: 99%

Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane

Heller

Martin

2014

Trans. Vis. Sci. Tech.

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Age-related macular degeneration (AMD) is the leading cause of legal blindness in older people in the developed world. The disease involves damage to the part of the retina responsible for central vision. Degeneration of retinal pigment epithelial (RPE) cells, photoreceptors, and choriocapillaris may contribute to visual loss. Over the past decades, scientists and clinicians have tried to replace lost RPE cells in patients with AMD using cells from different sources. In recent years, advances in generating RPE cells from stem cells have been made and clinical trials are currently evaluating the safety and efficiency of replacing the degenerated RPE cell layer with stem cellderived RPE cells. However, the therapeutic success of transplantation of stem cellderived RPE cells may be limited unless the transplanted cells can adhere and survive in the long term in the diseased eye. One hallmark of AMD is the altered extracellular environment of Bruch's membrane to which the grafted cells have to adhere. Here, we discuss recent approaches to overcome the inhibitory environment of the diseased eye and to enhance the survival rate of transplanted RPE cells. Our aim is to highlight novel approaches that may have the potential to improve the efficacy of RPE transplantation for AMD in the future.

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Use of MR Cell Tracking to Evaluate Targeting of Glial Precursor Cells to Inflammatory Tissue by Exploiting the Very Late Antigen-4 Docking Receptor

Cited by 46 publications

References 35 publications

Cell Size and Velocity of Injection are Major Determinants of the Safety of Intracarotid Stem Cell Transplantation

Cell Size and Velocity of Injection are Major Determinants of the Safety of Intracarotid Stem Cell Transplantation

Nanoparticles and clinically applicable cell tracking

Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane

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