scholarly journals A Tumbling Magnetic Microrobot System for Biomedical Applications

2020 ◽  
Author(s):  
Elizabeth E. Niedert ◽  
Chenghao Bi ◽  
Georges Adam ◽  
Elly Lambert ◽  
Luis Solorio ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Biomedical Applications ◽  
Imaging System ◽  
Ex Vivo ◽  
Negative Control ◽  
Circular Path ◽  
Rotational Axis ◽  
Significant Difference

AbstractA microrobot system comprised of an untethered tumbling magnetic microrobot, a two degree of freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a one hour time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

scholarly journals A Tumbling Magnetic Microrobot System for Biomedical Applications

Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 861
Author(s):  
Elizabeth E. Niedert ◽  
Chenghao Bi ◽  
Georges Adam ◽  
Elly Lambert ◽  
Luis Solorio ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Biomedical Applications ◽  
Imaging System ◽  
Ex Vivo ◽  
Negative Control ◽  
Circular Path ◽  
Rotational Axis ◽  
Significant Difference

A microrobot system comprising an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High-frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a 1-h time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

scholarly journals Proof of concept of a multimodal intravital molecular imaging system for tumour transpathology investigation

2021 ◽  
Author(s):  
Zhen Liu ◽  
Tao Cheng ◽  
Stephan Düwel ◽  
Ziying Jian ◽  
Geoffrey J. Topping ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Imaging System ◽  
Ex Vivo ◽  
Fiducial Markers ◽  
Proof Of Concept ◽  
Registration Accuracy ◽  
Microscopic Imaging ◽  
Window Chamber

Abstract Background Transpathology highlights the interpretation of the underlying physiology behind molecular imaging. However, it remains challenging due to the discrepancies between in vivo and in vitro measurements and difficulties of precise co-registration between trans-scaled images. This study aims to develop a multimodal intravital molecular imaging (MIMI) system as a tool for in vivo tumour transpathology investigation. Methods The proposed MIMI system integrates high-resolution positron imaging, magnetic resonance imaging (MRI) and microscopic imaging on a dorsal skin window chamber on an athymic nude rat. The window chamber frame was designed to be compatible with multimodal imaging and its fiducial markers were customized for precise physical alignment among modalities. The co-registration accuracy was evaluated based on phantoms with thin catheters. For proof of concept, tumour models of the human colorectal adenocarcinoma cell line HT-29 were imaged. The tissue within the window chamber was sectioned, fixed and haematoxylin–eosin (HE) stained for comparison with multimodal in vivo imaging. Results The final MIMI system had a maximum field of view (FOV) of 18 mm × 18 mm. Using the fiducial markers and the tubing phantom, the co-registration errors are 0.18 ± 0.27 mm between MRI and positron imaging, 0.19 ± 0.22 mm between positron imaging and microscopic imaging and 0.15 ± 0.27 mm between MRI and microscopic imaging. A pilot test demonstrated that the MIMI system provides an integrative visualization of the tumour anatomy, vasculatures and metabolism of the in vivo tumour microenvironment, which was consistent with ex vivo pathology. Conclusions The established multimodal intravital imaging system provided a co-registered in vivo platform for trans-scale and transparent investigation of the underlying pathology behind imaging, which has the potential to enhance the translation of molecular imaging.

An Innovative Ex Vivo Vascular Bioreactor as Comprehensive Tool to Study the Behavior of Native Blood Vessels Under Physiologically Relevant Conditions

2019 ◽  
Vol 2 (4) ◽  
Author(s):  
Noemi Vanerio ◽  
Marco Stijnen ◽  
Bas A. J. M. de Mol ◽  
Linda M. Kock
Keyword(s):  
Shear Stress ◽  
Blood Vessels ◽  
Ultrasound Imaging ◽  
Ex Vivo ◽  
Biological Response ◽  
Vessel Diameter ◽  
Tissue Growth ◽  
In Vivo Models

Abstract Ex vivo systems represent important models to study vascular biology and to test medical devices, combining the advantages of in vitro and in vivo models such as controllability of parameters and the presence of biological response, respectively. The aim of this study was to develop a comprehensive ex vivo vascular bioreactor to long-term culture and study the behavior of native blood vessels under physiologically relevant conditions. The system was designed to allow for physiological mechanical loading in terms of pulsatile hemodynamics, shear stress, and longitudinal prestretch and ultrasound imaging for vessel diameter and morphology evaluation. In this first experience, porcine carotid arteries (n = 4) from slaughterhouse animals were cultured in the platform for 10 days at physiological temperature, CO2 and humidity using medium with blood-mimicking viscosity, components, and stability of composition. As expected, a significant increase in vessel diameter was observed during culture. Flow rate was adjusted according to diameter values to reproduce and maintain physiological shear stress, while pressure was kept physiological. Ultrasound imaging showed that the morphology and structure of cultured arteries were comparable to in vivo. Histological analyses showed preserved endothelium and extracellular matrix and neointimal tissue growth over 10 days of culture. In conclusion, we have developed a comprehensive pulsatile system in which a native blood vessel can be cultured under physiological conditions. The present model represents a significant step toward ex vivo testing of vascular therapies, devices, drug interaction, and as basis for further model developments.

scholarly journals Cleaved CD31 as a target for in vivo molecular imaging of inflammation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jonathan Vigne ◽  
Sylvie Bay ◽  
Rachida Aid-Launais ◽  
Guillaume Pariscoat ◽  
Guillaume Rucher ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Molecular Form ◽  
Positive Control ◽  
Negative Control ◽  
Stability Study ◽  
Biodistribution Studies ◽  
Wide Range ◽  
Significant Difference

AbstractThere is a need for new targets to specifically localize inflammatory foci, usable in a wide range of organs. Here, we hypothesized that the cleaved molecular form of CD31 is a suitable target for molecular imaging of inflammation. We evaluated a bioconjugate of D-P8RI, a synthetic peptide that binds all cells with cleaved CD31, in an experimental rat model of sterile acute inflammation. Male Wistar rats were injected with turpentine oil into the gastrocnemius muscle two days before 99mTc-HYNIC-D-P8RI (or its analogue with L-Proline) SPECT/CT or [18F]FDG PET/MRI. Biodistribution, stability study, histology, imaging and autoradiography of 99mTc-HYNIC-D-P8RI were further performed. Biodistribution studies revealed rapid elimination of 99mTc-HYNIC-D-P8RI through renal excretion with almost no uptake from most organs and excellent in vitro and in vivo stability were observed. SPECT/CT imaging showed a significant higher 99mTc-HYNIC-D-P8RI uptake compared with its analogue with L-Proline (negative control) and no significant difference compared with [18F]FDG (positive control). Moreover, autoradiography and histology revealed a co-localization between 99mTc-HYNIC-D-P8RI uptake and inflammatory cell infiltration. 99mTc-HYNIC-D-P8RI constitutes a new tool for the detection and localization of inflammatory sites. Our work suggests that targeting cleaved CD31 is an attractive strategy for the specific in vivo imaging of inflammatory processes.

Trastuzumab versus MYL-1401O (a proposed trastuzumab biosimilar) in a phase I bioequivalence study: In vivo and in vitro immunomodulation.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 10-10
Author(s):  
Régine Audran ◽  
Haithem Chtioui ◽  
Anne-Christine Thierry ◽  
Carole Mayor ◽  
Laure Vallotton ◽  
...  
Keyword(s):  
Phase I ◽  
Mononuclear Cell ◽  
Ex Vivo ◽  
Reference Drug ◽  
Gm Csf ◽  
Significant Difference ◽  
Ifn Γ ◽  
The Impact

10 Background: Trastuzumab is a humanized monoclonal antibody targeting breast cancer cells overexpressing the HER2-oncoprotein. During a Phase-I single centre, single dose, randomized, double-blind, cross-over study assessing the bioequivalence of a proposed trastuzumab biosimilar (MYL-1401O) versus the initially marketed drug (Herceptin), we investigated in addition a large panel of pharmacodynamics parameters comparing the immunomodulatory activity of both drugs. Methods: 22 healthy males were included, 19 subjects receiving randomly a single intravenous infusion of MYL-1401O and 22 of Herceptin, separated by 16 to 22 week wash-out. Blood samples drawn pre- and post- infusion were assessed for in vivo serum cytokines induction (IL-1β, IL-2, IL-6, IL-10, IL-12, TNF-α, GM-CSF and IFN-γ) whereas the impact of treatment on mononuclear cell subsets and their level of activation was tested ex vivo. Volunteers’ PBMC (peripheral blood monocnuclear cells) were stimulated in vitro with recall antigens and mitogen for cytokine production. At baseline, we performed in addition a cytokine release assay on PBMC upon stimulation with trastuzumab as a preclinical safety test. Results: Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6h, and a modulation of mononuclear cell subset profile and level of activation. Notably CD16+ cells frequency decreased at 3h and peaked at 48h. Except for CD8+ T cells, there were no significant differences between Herceptin and its proposed biosimilar ex vivo. PBMC stimulated in vitro with trastuzumab secreted IL-6, TNF-a, IL-1β, GM-CSF, IFN-γ, and IL-10, but no IL-2. There was no significant difference between the two mAbs. Conclusions: Based on these in vivo, ex vivo and in vitro experiments, there is a strong assumption that MYL-1401O is biosimilar to the reference drug Herceptin for its immunomodulation properties as already proven for its bioequivalence. Clinical trial information: 2011-001406-94.

Survivin Is Required for Proliferation, but Not Polyploidization of Megakaryocytes.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1328-1328
Author(s):  
Jeremy Q Wen ◽  
Cindy Leung ◽  
Zan Huang ◽  
Sara Small ◽  
John Crispino
Keyword(s):  
Bone Marrow ◽  
Ex Vivo ◽  
Survivin Expression ◽  
Annexin V ◽  
Retroviral Infection ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Megakaryocyte Progenitors

Abstract Survivin is a member of chromosome passenger complex, which plays an important role in chromosome alignment, separation and cytokinesis. We recently reported that survivin is necessary for the proliferation and survival of hematopoietic stem and progenitor cells. Furthermore, we previously showed that reduced levels of survivin expression facilitates megakaryocyte development, whereas elevated levels of survivin inhibit their maturation and polyploidization. However, the extent to which survivin is necessary for polyploidization and terminal differentiation of committed megakaryocytes remains unclear. To determine whether survivin is required for megakaryocyte and platelet biogenesis, we mated mice with floxed alleles of survivin (sur fl/fl) to mice that express Cre recombinase under the control of the PF4 promoter. Compound mutant animals appeared grossly normal and harbored normal platelet counts. Furthermore, survivin deleted and control littermates displayed similar expression of CD41 and CD42, as well as similar DNA content within the CD41+ population. The only significant difference detected was an increase in annexin V staining of CD41+ cells within the bone marrow of the mice with survivin deletion. Analysis of DNA extracted from these bone marrows showed no evidence of the survivin deletion, indicating that the surviving cells all escaped excision. These in vivo findings are consistent with a requirement for survivin in the survival or proliferation of megakaryocyte progenitors. Next, to induce megakaryocyte development ex vivo, we cultured bone marrow from surv fl/fl mice in vitro in the presence of TPO. Using this approach, we were able to induce survivin deletion in 75% of the cells as evidenced by PCR. Despite the deletion of survivin, polyploidization of the ex vivo generated megakaryocytes was unaffected. Finally, we induced deletion of survivin by retroviral infection of surv fl/fl progenitors with MSCV-Cre and found that megakaryocyte polyploidization was actually increased in the excised population. Taken together, our results suggest that survivin is not required for polyploidization, but is necessary for proliferation of megakaryocyte progenitors.

scholarly journals Radioiodine labeling and in vivo trafficking of extracellular vesicles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chae Moon Hong ◽  
Prakash Gangadaran ◽  
Ji Min Oh ◽  
Ramya Lakshmi Rajendran ◽  
Arunnehru Gopal ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Extracellular Vesicles ◽  
Intravenous Injection ◽  
Gamma Camera ◽  
Imaging System ◽  
Ex Vivo ◽  
Nuclear Imaging ◽  
Significant Difference ◽  
Before And After

AbstractBiodistribution and role of extracellular vesicles (EVs) are still largely unknown. Reliable tracking methods for EVs are needed. In this study, nuclear imaging using radioiodine were developed and applied for tracking EVs derived from cell lines. EVs were obtained from supernatant of thyroid cancer cell (Cal62) and natural killer cells (NK92-MI) using sequential ultracentrifuges. Sulfosuccinimidyl-3-(4-hydroxypheynyl) propionate were labeled to membrane of Cal62 and NK92-MI cell derived EVs, then the EVs were labeled with radioiodine (I-131 and I-125) using pre-coated iodination tubes (RI-EVs). In vivo gamma camera images were obtained after intravenous injection of the RI-EVs, and ex vivo biodistribution study was also performed. EVs were labeled with radioiodine and radiochemical purity of the RI-EV was more than 98%. Results of nanoparticle tracking analysis and electron microscopy showed that there was no significant difference in EVs before and after the radioiodine labeling. After intravenous injection of RI-EVs to mice, gamma camera imaging well visualized the real-time biodistribution of the RI-EVs. RI-EVs were mainly visualized at liver, spleen, and lung. Nuclear imaging system of EVs derived from thyroid cancer and NK cells using radioiodine labeling of the EVs was established. Thus, this system might be helpful for in vivo tracking of EVs.

Direct and Continuous Inhibition of ADAM17 Using a Novel Selective Inhibitor Restores Functional Platelet Yield From Human Pluripotent Stem Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2323-2323
Author(s):  
Shinji Hirata ◽  
Ryoko Jono-Ohnishi ◽  
Satoshi Nishimura ◽  
Naoya Takayama ◽  
Sou Nakamura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Imaging System ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Human Platelets ◽  
P38 Map Kinase

Abstract Abstract 2323 Platelet transfusion is therapeutically important for patients with thrombocytopenia and/or bleeding disorders. Problems associated with a lack of donors and unknown infections in the blood have not been fully resolved, however. In that context, human induced pluripotent stem cells (hiPSCs) are a potentially abundant source of infection-free platelets. The pluripotent state of hiPSCs and their differentiation depend upon appropriate culture conditions defined in part by oxygen and temperature. We therefore initially examined whether temperatures at or below 24°C, which are required for preservation of platelet concentrates ex vivo, allow hiPSC differentiation to generate platelets. We found that only at 37°C were platelets generated. But at 37°C in vitro, platelets are subject to degradation exemplified by the shedding of GPIbα, a receptor for von Willebrand factor (vWF), which is caused by a disintegrin and metalloprotease (ADAM) 17. We therefore developed KP-457, a novel ADAM17 inhibitor that has a reverse hydroxamic acid structure and has been found safe in rats and dogs. Although inhibition of p38 MAP kinase, putatively upstream of ADAM17, reportedly inhibits GPIbα shedding in stored human platelets, even at 37°C, administration of the p38 inhibitor SB203580 induces cytotoxicity during differentiation, leading to a loss of platelet yield from hiPSCs. By contrast, KP-457 significantly protected GPIbα expression in platelets from hiPSCs and in aged human platelets in culture at 37°C. Moreover, iPSC-derived platelets generated in the presence of KP-457 displayed improved hemostatic function when studied using an imaging system that enables characterization of single-platelet kinetics during thrombus formation after laser-induced injury in vivo. We propose this new drug could markedly improve the maintenance of functional platelets generated in culture, particularly those derived from hiPSCs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hydrojet-based delivery of footprint-free iPSC-derived cardiomyocytes into porcine myocardium

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marbod Weber ◽  
Andreas Fech ◽  
Luise Jäger ◽  
Heidrun Steinle ◽  
Louisa Bühler ◽  
...  
Keyword(s):  
Imaging System ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Pressure Setting ◽  
Infarcted Myocardium ◽  
Efficient Delivery ◽  
Intramyocardial Delivery ◽  
Induced Pluripotent

Abstract The reprogramming of patient´s somatic cells into induced pluripotent stem cells (iPSCs) and the consecutive differentiation into cardiomyocytes enables new options for the treatment of infarcted myocardium. In this study, the applicability of a hydrojet-based method to deliver footprint-free iPSC-derived cardiomyocytes into the myocardium was analyzed. A new hydrojet system enabling a rapid and accurate change between high tissue penetration pressures and low cell injection pressures was developed. Iron oxide-coated microparticles were ex vivo injected into porcine hearts to establish the application parameters and the distribution was analyzed using magnetic resonance imaging. The influence of different hydrojet pressure settings on the viability of cardiomyocytes was analyzed. Subsequently, cardiomyocytes were delivered into the porcine myocardium and analyzed by an in vivo imaging system. The delivery of microparticles or cardiomyocytes into porcine myocardium resulted in a widespread three-dimensional distribution. In vitro, 7 days post-injection, only cardiomyocytes applied with a hydrojet pressure setting of E20 (79.57 ± 1.44%) showed a significantly reduced cell viability in comparison to the cells applied with 27G needle (98.35 ± 5.15%). Furthermore, significantly less undesired distribution of the cells via blood vessels was detected compared to 27G needle injection. This study demonstrated the applicability of the hydrojet-based method for the intramyocardial delivery of iPSC-derived cardiomyocytes. The efficient delivery of cardiomyocytes into infarcted myocardium could significantly improve the regeneration.

scholarly journals Potensi Bacillus licheniformis dan Streptomyces olivaceoviridis sebagai Penghambat Pertumbuhan Jamur Saprolegnia sp. Penyebab Saprolegniasis pada Ikan secara In Vitro [Potential of Bacillus licheniformis and Streptomyces olivaceoviridis as Inhibiting The Growth of Fungus Saprolegnia sp, Cause Saprolegniasis on Fish by Using In Vitro]

2019 ◽  
Vol 7 (2) ◽  
pp. 133
Author(s):  
Oktantia Frenny Anggani ◽  
Rahayu Kusdarwati ◽  
Hari Suprapto
Keyword(s):  
Bacillus Licheniformis ◽  
Inhibition Zone ◽  
Positive Control ◽  
Negative Control ◽  
Randomized Design ◽  
Significant Difference ◽  
Streptomyces Olivaceoviridis ◽  
Tukey Honestly Significant Difference

Abstract Saprolegniasis is a fungal disease on fish caused by Saprolegnia sp, which is saprophyte, damaging healthy tissue and makes the immune system in fish deacreased. The uniquennes of Saprolegnia sp has the main components of the cell wall in the form of chitin that was instrumental in shaping the structure of the tip growth of fungal hyphae. Control of fungal pathogenic Saprolegnia sp can use chitinolytic microorganisms based on ability to produce chitinase for example using bacteria. This study aims to potential of Bacillus licheniformis and Streptomyces olivaceoviridis as inhibiting the growth of fungus Saprolegnia sp, cause saprolegniasis on fish by using in vitro. The research method is experimental with completely randomized design (CRD), which consists of four treatments with five replications. The experimental used is A (Saprolegnia sp and Bacillus licheniformis), B (Saprolegnia sp and Streptomyces olivaceoviridis), C negative control (Saprolegnia sp) and D positive control (Saprolegnia sp and Ketokonazol 2 %). The main parameters measured were observed inhibition zone on each treatment. Supporting parameters were observed is an observation of abnormal hpyphae structure after being induced by bacteria Bacillus licheniformis dan Streptomyces olivaceoviridis. Data were analyzed using analysis of variants (ANOVA) and to know the difference between treatments were determined by Tukey honestly significant difference (Tukey HSD) Test. The results showed that the potential of chitinolytic Bacillus licheniformis can provide a good barrier of 4,62 cm by 5,48 cm compared Streptomyces olivaceoviridis in inhibiting the growth Saprolegnia sp. Suggestions in this research is the need to further research on the value of chitinase Bacillus licheniformis and Streptomyces olivaceoviridis. Further research by using in vivo.

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