Differences in clotting parameters between species for preclinical large animal studies of cardiovascular devices

2017 ◽  
Vol 21 (2) ◽  
pp. 138-141 ◽  
Author(s):  
Toshihide Mizuno ◽  
Tomonori Tsukiya ◽  
Yoshiaki Takewa ◽  
Eisuke Tatsumi
Keyword(s):  
Animal Studies ◽  
Large Animal ◽  
Cardiovascular Devices

Abstract P469: Scale-up And Characterization Of Therapeutic Mesenchymal Stromal Cell-derived Extracellular Vesicles

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Selen Uman ◽  
Jason A Burdick
Keyword(s):  
Cell Culture ◽  
Extracellular Vesicles ◽  
Animal Studies ◽  
Scale Up ◽  
Spinner Flask ◽  
Perfusion Bioreactor ◽  
Large Animal ◽  
Culture Methods ◽  
Therapeutic Benefits ◽  
Cell Culture Methods

Introduction: Early studies have shown therapeutic benefits of mesenchymal stromal cells (MSCs) in cardioprotection due to their angiogenic, proliferative, anti-apoptotic and anti-inflammatory properties, which are now attributed to secreted factors such as extracellular vesicles (EVs). While MSC-EVs have shown promise in small animals for cardiovascular therapies, large animal studies are required to evaluate the therapeutic benefit of MSC-EVs for clinical translation. One of the biggest challenges for large animal studies is the need to generate clinically-relevant quality and quantity of EVs without batch-to-batch variations that could compromise efficacy. This study aims to explore three different cell culture methods (traditionally-used tissue culture plates (TCP), 3-D printed bioscaffolds in a perfusion system (P), and microcarriers in dynamic spinner flask conditions (M)) to scale-up the production of MSC-EVs across four different biological donors and rigorously investigate EV yield, size, shape, and content. Methods: MSCs were isolated from the iliac crest of four different Yucatan minipigs using heparinized syringes, and cells were expanded to passage four, at which point they were seeded onto the respective cell culture methods. EVs were collected from conditioned medium (CM) via differential ultracentrifugation. EV size, distribution, yield, and protein concentration were studied using Nanoparticle Tracking Analysis (NTA) and microBCA assays. Results: Both perfusion bioreactor and spinner flask systems enabled sustained maintenance of large numbers of cells. Across biological donors and fabrication methods, modes remained within 50-150 nm and were not statistically different. Microcarrier-based spinner flasks and perfusion bioreactor set-ups both improved EV yield, up to 6 times in efficiency. Ongoing research focuses on examining differences in EV content across biological donors using RNA-sequencing and proteomics.

scholarly journals Large Animal Studies to Reduce the Foreign Body Reaction in Brain–Computer Interfaces: A Systematic Review

Biosensors ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 275
Author(s):  
Shan Yasin Mian ◽  
Jonathan Roy Honey ◽  
Alejandro Carnicer-Lombarte ◽  
Damiano Giuseppe Barone
Keyword(s):  
Foreign Body ◽  
Animal Studies ◽  
Foreign Body Reaction ◽  
Inflammatory Cells ◽  
Anatomical Location ◽  
Large Animal ◽  
Brain Computer Interfaces ◽  
Computer Interfaces ◽  
Electrode Insertion

Brain–computer interfaces (BCI) are reliant on the interface between electrodes and neurons to function. The foreign body reaction (FBR) that occurs in response to electrodes in the brain alters this interface and may pollute detected signals, ultimately impeding BCI function. The size of the FBR is influenced by several key factors explored in this review; namely, (a) the size of the animal tested, (b) anatomical location of the BCI, (c) the electrode morphology and coating, (d) the mechanics of electrode insertion, and (e) pharmacological modification (e.g., drug eluting electrodes). Trialing methods to reduce FBR in vivo, particularly in large models, is important to enable further translation in humans, and we systematically reviewed the literature to this effect. The OVID, MEDLINE, EMBASE, SCOPUS and Scholar databases were searched. Compiled results were analysed qualitatively. Out of 8388 yielded articles, 13 were included for analysis, with most excluded studies experimenting on murine models. Cats, rabbits, and a variety of breeds of minipig/marmoset were trialed. On average, over 30% reduction in inflammatory cells of FBR on post mortem histology was noted across intervention groups. Similar strategies to those used in rodent models, including tip modification and flexible and sinusoidal electrode configurations, all produced good effects in histology; however, a notable absence of trials examining the effect on BCI end-function was noted. Future studies should assess whether the reduction in FBR correlates to an improvement in the functional effect of the intended BCI.

Similar effect of autologous and allogeneic cell therapy for ischemic heart disease: results from a meta-analysis of large animal studies

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P1462-P1462
Author(s):  
S. J. Jansen Of Lorkeers ◽  
J. E. C. Eding ◽  
T. I. G. Van Der Spoel ◽  
H. M. Vesterinen ◽  
S. Koudstaal ◽  
...  
Keyword(s):  
Heart Disease ◽  
Cell Therapy ◽  
Ischemic Heart Disease ◽  
Animal Studies ◽  
Meta Analysis ◽  
Ischemic Heart ◽  
Large Animal ◽  
Allogeneic Cell ◽  
Allogeneic Cell Therapy

scholarly journals Impact of guidance documents on translational large animal studies of cartilage repair

2015 ◽  
Vol 7 (310) ◽  
pp. 310re9-310re9 ◽  
Author(s):  
Christian G. Pfeifer ◽  
Matthew B. Fisher ◽  
James L. Carey ◽  
Robert L. Mauck
Keyword(s):  
Cartilage Repair ◽  
Animal Studies ◽  
Large Animal ◽  
Guidance Documents

scholarly journals Clinical protocol levels are required in laboratory animal surgery when using medical devices: experiences with ureteral replacement surgery in goats

2017 ◽  
Vol 51 (5) ◽  
pp. 538-541 ◽  
Author(s):  
Paul K. J. D. de Jonge ◽  
Marije Sloff ◽  
Heinz P. Janke ◽  
Barbara B. M. Kortmann ◽  
Robert P. E. de Gier ◽  
...  
Keyword(s):  
Medical Devices ◽  
Stent Placement ◽  
Animal Studies ◽  
Large Animal ◽  
Short Report ◽  
Clinical Protocols ◽  
Replacement Surgery ◽  
Iodinated Contrast ◽  
Tissue Reconstruction ◽  
Animal Surgery

It is common to test medical devices in large animal studies that are or could also be used in humans. In this short report we describe the use of a ureteral J-stent for the evaluation of biodegradable tubular constructs for tissue reconstruction, and the regeneration of ureters in Saanen goats. Similarly to a previous study in pigs, the ureteral J-stent was blindly inserted until some resistance was met. During evaluation of the goats after three months, perforation of the renal cortex by the stent was observed in four out of seven animals. These results indicated that blind stent placement was not possible in goats. In four new goats, clinical protocols were followed using X-ray and iodinated contrast fluids to visualize the kidney and stent during stent placement. With this adaptation the stents were successfully placed in the kidneys of these four new goats with minimal additional effort. It is likely that other groups in other fields ran into similar problems that could have been avoided by following clinical protocols. Therefore, we would like to stress the importance of following clinical protocols when using medical devices in animals to prevent unnecessary suffering and to reduce the number of animals needed.

scholarly journals Establishment and Characterization of a Multi-Purpose Large Animal Exposure Chamber for Investigating Health Effects

2018 ◽  
Author(s):  
Xinze Peng ◽  
Mia R. Maltz ◽  
Jon K. Botthoff ◽  
Emma L. Aronson ◽  
Tara M. Nordgren ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Animal Studies ◽  
Exposure Chamber ◽  
Whole Body ◽  
Large Animal ◽  
Uniform Dispersion ◽  
Health Studies ◽  
Animal Exposure

Air pollution poses a significant threat to the environment and human health. Most in-vivo health studies conducted regarding air pollutants, including particulate matter (PM) and gas phase pollutants, have been either through traditional medical intranasal treatment or using a tiny chamber, which limit animal activities. In this study, we designed and tested a large, whole-body, multiple animal exposure chamber with uniform dispersion and exposure stability for animal studies. The chamber simultaneously controls particle size distribution and PM mass concentration. Two different methods were used to generate aerosol suspension through either soluble material (Alternaria extract), liquid particle suspension (Nanosilica solution) or dry powder (silica powder). We demonstrate that the chamber system provides well controlled and characterized whole animal exposures, where dosage is by inhalation of particulate matter.

scholarly journals Effect of Bone Marrow Mesenchymal Stromal Cell Therapies in Rodent Models of Sepsis: A Meta-Analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Lite Ge ◽  
Jing Zhao ◽  
Huiyin Deng ◽  
Chunli Chen ◽  
Zhiping Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Fixed Effects ◽  
Animal Studies ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Large Animal ◽  
Significant Heterogeneity ◽  
Rodent Models ◽  
Inclusion Criteria ◽  
Knowledge Gaps

BackgroundMultiple preclinical studies have demonstrated that bone‐marrow derived mesenchymal stromal (stem) cells [MSC(M)] positively influence the severity of sepsis symptoms and mortality in rodent models. However, this remains an inconclusive finding.ObjectiveTo review the effect of naïve MSC(M) in rodent models of sepsis.MethodsThe PubMed, EMBASE, and Web of Science databases were searched up to August 31, 2021. Inclusion criteria according to PICOS criteria were as follows: (1) population: rodents; (2) intervention: unmodified MSC(M); (3) comparison: not specified; (4) primary outcome: the effects of MSC(M) cell therapy on the mortality of rodent models of sepsis and endotoxemia; (5) study: experimental studies. Multiple prespecified subgroup and meta-regression analysis were conducted. Following quality assessment, random effects models were used for this meta-analysis.The inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs).Resultstwenty-four animal studies met the inclusion criteria. Our results revealed an overall OR difference between animals treated with naïve MSC(M) and controls for mortality rate was 0.34(95% confidence interval: 0.27-0.44; P < 0.0001). Significant heterogeneity among studies was observed.ConclusionsThe findings of this meta-analysis suggest that naïve MSC(M) therapy decreased mortality in rodent models of sepsis. Additionally, we identified several key knowledge gaps, including the lack of large animal studies and uncertainty regarding the optimal dose of MSC(M) transplantation in sepsis. Before MSC(M) treatment can advance to clinical trials, these knowledge gaps must be addressed.

Dependence of Intervertebral Disc Pressure Generation on Load History

2009 ◽  
Author(s):  
David Hwang ◽  
Miao Yu ◽  
Adam H. Hsieh
Keyword(s):  
Intervertebral Disc ◽  
Animal Studies ◽  
Sensor Technology ◽  
Laboratory Model ◽  
Large Animal ◽  
Pressure Measurements ◽  
Load History ◽  
Local Stresses ◽  
History Of ◽  
Rat Tail

It has been thoroughly documented that low back pain is often associated with deregulated biological function and compromised mechanical behavior of the intervertebral disc. Therefore, intervertebral disc mechanics have long been thought of as important factors both in driving cell-mediated processes involved in degeneration and in distinguishing between healthy versus degenerate discs. The nucleus pulposus is an integral part of the mechanics of the disc, the key property being its ability to pressurize to resist and distribute compressive stress to the annulus fibrosus and the endplates. There has been a history of intradiscal pressure measurements in cadaveric as well as large animal studies; however, these studies have focused on the consequences of degeneration or the change in stress distribution by varying spinal orientations. In order to be able to relate local stresses induced in discs to changes in cellular function, such pressure measurements must be obtained from an animal model amenable to chronic disc loading. Rat tail discs have been one widely used laboratory model, but the discs are too small for measuring load-induced nucleus pressures using current sensor technology.

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