Publications by authors named "Dalis E Collins"

8 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

Poxvirus Infection in a Colony of Laboratory Pigeons ().

Comp Med 2019 05 18;69(3):179-183. Epub 2019 Mar 18.

Center for Comparative Medicine, Baylor College of Medicine, Houston, Texas.

Pigeons () are used in biomedical research for studies of vision, cognition, neuronal pathways, and spatial orientation. Because there are few commercial laboratory sources, research pigeons are typically acquired from local fancier breeders or bred onsite. For acquired pigeons, the health and vaccine status is often unknown. A juvenile pigeon, born onsite and living in an enclosed outdoor loft, presented with small, bleeding, wart-like lesions on the medial aspects of digits 1 and 4. Topical treatment was initiated. Within a week, 4 fledglings were reported for small, dark papular lesions on the face, head, neck, and beak, and shortly thereafter, 2 additional juvenile pigeons developed similar lesions. The fledglings were euthanized, and histologic examination revealed numerous intralesional eosinophilic cytoplasmic viral inclusions (Bollinger bodies) confirming a diagnosis of poxvirus infection, likely pigeon pox. Although usually self-limiting, pigeon pox can cause moderate to severe lesions in fledgling and juvenile birds. Vaccination with a modified live poxvirus labeled for chickens was used to create herd immunity to pigeon poxvirus. Since vaccination of our entire flock and implementation of more stringent health protocols, all lesions have resolved, and no new lesions have been noted.
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http://dx.doi.org/10.30802/AALAS-CM-18-000074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591677PMC
May 2019

A new set of eyes: development of a novel microangioscope for neurointerventional surgery.

J Neurointerv Surg 2019 Oct 16;11(10):1036-1039. Epub 2019 Mar 16.

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

Background: Endovascular technological advances have revolutionized the field of neurovascular surgery and have become the mainstay of treatment for many cerebrovascular pathologies. Digital subtraction angiography (DSA) is the 'gold standard' for visualization of the vasculature and deployment of endovascular devices. Nonetheless, with recent technological advances in optics, angioscopy has emerged as a potentially important adjunct to DSA. Angioscopy can offer direct visualization of the intracranial vasculature, and direct observation and inspection of device deployment. However, previous iterations of this technology have not been sufficiently miniaturized or practical for modern neurointerventional practice.

Objective: To describe the evolution, development, and design of a microangioscope that offers both high-quality direct visualization and the miniaturization necessary to navigate in the small intracranial vessels and provide examples of its potential applications in the diagnosis and treatment of cerebrovascular pathologies using an in vivo porcine model.

Methods: In this proof-of-concept study we introduce a novel microangioscope, designed from coherent fiber bundle technology. The microangioscope is smaller than any previously described angioscope, at 1.7 F, while maintaining high-resolution images. A porcine model is used to demonstrate the resolution of the images in vivo.

Results: Video recordings of the microangioscope show the versatility of the camera mounted on different microcatheters and its ability to navigate external carotid artery branches. The microangioscope is also shown to be able to resolve the subtle differences between red and white thrombi in a porcine model.

Conclusion: A new microangioscope, based on miniaturized fiber optic technology, offers a potentially revolutionary way to visualize the intracranial vascular space.
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http://dx.doi.org/10.1136/neurintsurg-2018-014610DOI Listing
October 2019

Viral Vector Biosafety in Laboratory Animal Research.

Comp Med 2017 Jun;67(3):215-221

University of Michigan, Ann Arbor, Michigan;, Email:

Viral vector research presents unique occupational health and safety challenges to institutions due to the rapid development of both in vivo and in vitro gene-editing technologies. Risks to human and animal health make it incumbent on institutions to appropriately evaluate viral vector usage in research on the basis of available information and governmental regulations and guidelines. Here we review the factors related to risk assessment regarding viral vector usage in animals and the relevant regulatory documents associated with this research, and we highlight the most commonly used viral vectors in research today. This review is particularly focused on the background, use in research and associated health and environmental risks related to adenoviral, adeno-associated viral, lentiviral, and herpesviral vectors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482513PMC
June 2017

Ventricular Parasystole in a Neonatal Rhesus Macaque ().

Comp Med 2016 12;66(6):489-493

Division of Comparative Medicine, Oregon National Primate Research Center, Beaverton, Oregon.

A 6-d-old Indian-origin female rhesus macaque (Macaca mulatta) presented with bradycardia shortly after sedation with ketamine. No other cardiac abnormalities were apparent. Approximately 2 wk after the initial presentation, the macaque was again bradycardic and exhibited a regularly irregular arrhythmia on a prestudy examination. ECG, echocardiography, blood pressure measurement, SpO2 assessment, and a CBC analysis were performed. The echocardiogram and bloodwork were normal, but the infant was hypotensive at the time of echocardiogram. The ECG revealed ventricular parasystole. Ventricular parasystole is considered a benign arrhythmia caused by an ectopic pacemaker that is insulated from impulses from the sinus node. Given this abnormality, the macaque was transferred to a short-term study protocol, according to veterinary recommendation. On the final veterinary exam, a grade 3 systolic murmur and a decrease in arrhythmia frequency were noted. Gross cardiac lesions were not identified at necropsy the following day. Cardiac tissue sections were essentially normal on microscopic examination. This infant did not display signs of cardiovascular insufficiency, and a review of the medical record indicated normal growth, feed intake and activity levels. This case demonstrates the importance of appropriate screening of potential neonatal and juvenile research candidates for occult cardiovascular abnormalities. Whether the arrhythmia diagnosed in this case was truly innocuous is unclear, given the documented hypotension and the development of a systolic heart murmur.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157965PMC
December 2016

Clinical Assessment of Urinary Tract Damage during Sustained-Release Estrogen Supplementation in Mice.

Comp Med 2017 02;67(1):11-21

Unit for Laboratory Animal Medicine (ULAM), University of Michigan, Ann Arbor, Michigan;, Email:

Estrogen supplementation is a key component of numerous mouse research models but can adversely affect the urinary system. The goal of this study was to develop a clinical scoring system and identify biomarkers of occult urinary tract lesions prior to the development of systemic illness in mice. Ovariectomized or sham-surgery SCID mice were implanted subcutaneously with a placebo pellet or one containing sustained-release estradiol (0.18 mg 60-d release 17β-estradiol). Mice were assessed twice weekly for 4 to 6 wk by using a clinical scoring system that included body condition, general activity, posture, hair coat, hydration, abdominal distension, urine staining of coat and skin, and ability to urinate. Samples were collected weekly for urinalysis, BUN, creatinine, and serum estradiol levels. Terminal samples were analyzed for histopathologic lesions. Compared with placebo controls, estradiolsupplemented mice had higher serum estradiol levels at weeks 2 and 3; significant differences in total clinical scores by the 3-wk time point; and in body condition, general activity, posture, hair coat, and urine staining scores by the 6-wk terminal time point. Urinary tract lesions included hydronephrosis, pyelonephritis, cystitis, and urolithiasis. All mice with urolithiasis had crystalluria, and 5 of the 6 mice with pyelonephritis or hydroureter had dilute urine (that is, specific gravity less than 1.030). However, these findings were not specific to mice with lesions. A total clinical score of 3.5 (maximum, 24) identified estradiol-supplemented mice with 83% specificity and 50% sensitivity, but no single clinical parameter, biomarker, or the total clinical score accurately predicted occult urinary tract lesions. Considering the lesions we observed, prudence is warranted when using pelleted sustained-release estradiol in mice, and important parameters to monitor for animal health include urine staining, body condition score, urine sediment, and urine specific gravity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310620PMC
February 2017

Choosing a non-traditional path.

Authors:
Dalis E Collins

Lab Anim (NY) 2015 Oct;44(10):413

Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI.

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http://dx.doi.org/10.1038/laban.858DOI Listing
October 2015

Spontaneous Dilated Cardiomyopathy and Right-Sided Heart Failure as a Differential Diagnosis for Hepatosis Dietetica in a Production Pig.

Comp Med 2015 Aug;65(4):327-32

Unit for Laboratory Animal Medicine, In-Vivo Animal Core, University of Michigan Medical School, Ann Arbor, Michigan, USA.

An experimentally naïve 37.7-kg Yorkshire-crossbred gilt died unexpectedly 2 d after arrival. Necropsy revealed severe dilated cardiomyopathy characterized grossly by markedly dilated ventricles and thinned ventricular walls and interventricular septum. Histologically there was multifocal myofiber attenuation and patchy loss of myofiber cross striations. The liver contained submassive to massive, diffuse hepatic centrilobular hemorrhage and degeneration. These lesions supported a diagnosis of dilated cardiomyopathy with right heart failure and secondary hepatic degeneration due to marked acute passive congestion. To our knowledge, this case is the first report of spontaneous dilated cardiomyopathy in swine and represents a potential diagnostic challenge regarding the differentiation of the cardiac-associated liver lesion from hepatosis dietetica. The diagnosis of dilated cardiomyopathy and right-sided heart failure was supported by the character of the hepatic lesion, absence of typical gross or histologic lesions of mulberry heart disease, and normal selenium levels.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549678PMC
August 2015