Publications by authors named "Kevin M Camstra"

5 Publications

  • Page 1 of 1

Endovascular Selective Intra-Arterial Infusion of Mesenchymal Stem Cells Loaded With Delta-24 in a Canine Model.

Neurosurgery 2020 12;88(1):E102-E113

Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.

Background: Delta-24-RGD, an oncolytic adenovirus, shows promise against glioblastoma. To enhance virus delivery, we recently demonstrated that human bone marrow-derived mesenchymal stem cells loaded with Delta-24-RGD (hMSC-D24) can eradicate glioblastomas in mouse models. There are no studies examining the safety of endovascular selective intra-arterial (ESIA) infusions of MSC-D24 in large animals simulating human clinical situations.

Objective: To perform canine preclinical studies testing the feasibility and safety of delivering increasing doses of hMSCs-D24 via ESIA infusions.

Methods: ESIA infusions of hMSC-D24 were performed in the cerebral circulation of 10 normal canines in the target vessels (internal carotid artery [ICA]/P1) via transfemoral approach using commercially available microcatheters. Increasing concentrations of hMSC-D24 or particles (as a positive control) were injected into 1 hemisphere; saline (negative control) was infused contralaterally. Toxicity (particularly embolic stroke) was assessed on postinfusion angiography, diffusion-weighted magnetic resonance imaging, clinical exam, and necropsy.

Results: ESIA injections were performed in the ICA (n = 7) or P1 (n = 3). In 2 animals injected with particles (positive control), strokes were detected by all assays. Of 6 canines injected with hMSC-D24 through the anterior circulation, escalating dose from 2 × 106 cells/20 mL to 1 × 108 cells/10 mL resulted in no strokes. Two animals had ischemic and hemorrhagic strokes after posterior cerebral artery catheterization. A survival experiment of 2 subjects resulted in no complications detected for 24-h before euthanization.

Conclusion: This novel study simulating ESIA infusion demonstrates that MSCs-D24 can be infused safely at least up to doses of 1 × 108 cells/10 mL (107 cells/ml) in the canine anterior circulation using commercially available microcatheters. These findings support a clinical trial of ESIA infusion of hMSCs-D24.
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http://dx.doi.org/10.1093/neuros/nyaa470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735865PMC
December 2020

Canine Model for Selective and Superselective Cerebral Intra-Arterial Therapy Testing.

Neurointervention 2020 Nov 11;15(3):107-116. Epub 2020 Aug 11.

Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.

Purpose: With advancing endovascular technology and increasing interest in minimally invasive intra-arterial therapies such as stem cell and chemotherapy for cerebral disease, the establishment of a translational model with cerebral circulation accessible to microcatheters is needed. We report our experience catheterizing canine cerebral circulation with microcatheters, present high-resolution angiographic images of the canine vascular anatomy, describe arterial branch flow patterns and provide measurements of canine arterial conduits.

Materials And Methods: Angiograms were performed on 10 intact purpose-bred hounds. Angiography, measurements of arterial conduits and catheterization information for intracranial arterial branches were obtained.

Results: Selective and superselective cerebral angiography was successful in all subjects. Relevant arterial mean diameters include the femoral (4.64 mm), aorta (9.38 mm), external carotid (3.65 mm), internal carotid arteries (1.6 mm), vertebrobasilar system and Circle of Willis branches. Catheterization of the Circle of Willis was achieved via the posterior circulation in all subjects tested (n=3) and the use of flow directed microcatheters resulted in reduced arterial tree deformation and improved superselection of intracranial vessels. Catheterization of the intracranial circulation was attempted but not achieved via the internal carotid artery (n=7) due to its tortuosity and subsequent catheter related vasospasm.

Conclusion: The canine cerebral vasculature is posterior circulation dominant. Anterior circulation angiography is achievable via the internal carotid artery, but direct cerebral arterial access is best achieved via the posterior circulation using flow-directed microcatheters. It is feasible to deliver intra-arterial therapies to selective vascular territories within the canine cerebral circulation, thus making it a viable animal model for testing novel intra-arterial cerebral treatments.
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http://dx.doi.org/10.5469/neuroint.2020.00150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608496PMC
November 2020

Microcatheter delivery of neurotherapeutics: compatibility with mesenchymal stem cells.

J Neurosurg 2019 Sep 6:1-9. Epub 2019 Sep 6.

Departments of1Neurosurgery and.

Objective: Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) have been used in clinical trials for the treatment of several neurological disorders. MSCs have been explored as a delivery modality for targeted viral therapeutic agents in the treatment of intracranial pathologies. Delta-24-RGD, a tumor-selective oncolytic adenovirus designed to target malignant glioma cells, has been shown to be effective in animal models and in a recent clinical trial. However, the most efficient strategy for delivering oncolytic therapies remains unclear. BM-hMSCs have been shown to home toward glioma xenografts after intracarotid delivery. The feasibility of selective intraarterial infusion of BM-hMSCs loaded with Delta-24-RGD (BM-hMSC-Delta-24) to deliver the virus to the tumor is being investigated. To evaluate the feasibility of endovascular intraarterial delivery, the authors tested in vitro the compatibility of BM-hMSC-Delta-24 with a variety of commercially available, clinically common microcatheters.

Methods: BM-hMSCs were cultured, transfected with Delta-24-RGD, and resuspended in 1% human serum albumin. The solution was then injected via 4 common neuroendovascular microcatheters of different inner diameters (Marathon, Echelon-14, Marksman, and SL-10). Cell count and viability after injection through the microcatheters were assessed, including tests of injection velocity and catheter configuration. Transwell assays were performed with the injected cells to test the efficacy of BM-hMSC-Delta-24 activity against U87 glioma cells. BM-hMSC-Delta-24 compatibility was also tested with common neuroendovascular medications: Omnipaque, verapamil, and heparin.

Results: The preinfusion BM-hMSC-Delta-24 cell count was 1.2 × 105 cells/ml, with 98.7% viability. There was no significant difference in postinfusion cell count or viability for any of the catheters. Increasing the injection velocity from 1.0 ml/min to 73.2 ml/min, or modifying the catheter shape from straight to tortuous, did not significantly reduce cell count or viability. Cell count and viability remained stable for up to 5 hours when the cell solution was stored on ice. Mixing BM-hMSC-Delta-24 with clinical concentrations of Omnipaque, verapamil, and heparin prior to infusion did not alter cell count or viability. Transwell experiments demonstrated that the antiglioma activity of BM-hMSC-Delta-24 was maintained after infusion.

Conclusions: BM-hMSC-Delta-24 is compatible with a wide variety of microcatheters and medications commonly used in neuroendovascular therapy. Stem cell viability and viral agent activity do not appear to be affected by catheter configuration or injection velocity. Commercially available microcatheters can be used to deliver stem cell neurotherapeutics via intraarterial routes.
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http://dx.doi.org/10.3171/2019.6.JNS19327DOI Listing
September 2019

Optimizing contrast-enhanced cone-beam CT protocol to facilitate simultaneous visualization of neurovascular pathologies and surrounding structures of interest.

Interv Neuroradiol 2019 Feb 19;25(1):102-110. Epub 2018 Sep 19.

1 Department of Neurosurgery, Baylor College of Medicine, Houston, USA.

Objective: Contrast-enhanced cone-beam computed tomography (CBCT) imaging is commonly used for evaluating neurovascular stents and their relationship to the parent artery or vascular pathologies such as arteriovenous malformations (AVMs) and dural arteriovenous fistulas (dAVFs) in the context of surrounding anatomical structures. The purpose of this study was to understand the effects of varying concentrations of contrast medium used in CBCT imaging for optimal visualization of various endovascular devices and anatomical pathologies.

Methods: Thirty-five patients with various neurovascular pathologies were included in the study. Contrast-enhanced CBCT images (20 s DR, Siemens syngo DynaCT, Siemens AG, Forchheim, Germany) were acquired in all cases, with varying dilutions of contrast medium, from 1% to 30%. The injection rate was kept constant at 3 cc/sec with an X-ray delay of two sec, and a total volume of 66 cc of diluted contrast was administered. Results from visual and quantitative analysis were reported.

Results: Ten percent dilution of contrast medium resulted in the best image differentiation between flow-diverter devices and the parent artery. Concentrations as low as 2.5% contrast medium also resulted in identifying AVMs in the context of the surrounding brain parenchyma, whereas 20% to 30% dilution provided the best visualization of residual AVMs with prior Onyx embolization and dAVFs in the presence of bony structures.

Conclusions: Simultaneous visualization of brain parenchyma, bony structures, devices, and pathological anatomy using contrast-enhanced CBCT imaging is feasible with appropriate doses of iodinated contrast, and should be tailored to the individual case based on the goals of CBCT.
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http://dx.doi.org/10.1177/1591019918800216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378524PMC
February 2019

Development of a recalcitrant, large clot burden, bifurcation occlusion model for mechanical thrombectomy.

Neurosurg Focus 2017 Apr;42(4):E6

Departments of 1 Neurosurgery and.

OBJECTIVE Stroke is a major cause of disability and death in adults. Several large randomized clinical trials have shown the significant benefit of mechanical thrombectomy with modern stent retrievers in the treatment of large-vessel occlusions. However, large clots located at bifurcations remain challenging to treat. An in vivo model of these recalcitrant clots needs to be developed to test future generations of devices. METHODS Autologous blood was drawn from anesthetized swine via a femoral sheath. Blood was then mixed with thrombin, calcium chloride, and saline, and injected into silicone tubing to form cylindrical clots in the standard fashion. Matured clots were then delivered in an unfragmented fashion directly into the distal extracranial vasculature, at branch points where vessel sizes mimic the human middle cerebral artery, by using Penumbra aspiration tubing and the Penumbra ACE68 reperfusion catheter. RESULTS A total of 5 adult swine were used to develop the model. The techniques evolved during experiments in the first 3 animals, and the last 2 were used to establish the final model. In these 2 swine, a total of 8 autologous clots, 15-20 mm, were injected directly into 8 distal extracranial vessels at branch points to mimic a bifurcation occlusion in a human. All clots were delivered directly at a distal bifurcation or trifurcation in an unfragmented fashion to cause an occlusion. Ten revascularization attempts were made, and none of the branch-point occlusions were fully revascularized on the first attempt. CONCLUSIONS Using novel large-bore distal access catheters, large unfragmented clots can be delivered into distal extracranial vessels in a swine occlusion model. The model mimics the clinical situation of a recalcitrant bifurcation occlusion and will be valuable in the study of next-generation stroke devices and in training settings.
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http://dx.doi.org/10.3171/2017.1.FOCUS16501DOI Listing
April 2017