scholarly journals Multipotent Stromal Cell Extracellular Vesicle Distribution in Distant Organs after Introduction into a Bone Tissue Defect of a Limb

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 306
Author(s):  
Igor Maiborodin ◽  
Aleksandr Shevela ◽  
Michael Toder ◽  
Sergey Marchukov ◽  
Natalya Tursunova ◽  
...  

When administered intravenously, extracellular vesicles derived from multipotent stromal cells (MSC EVs) immediately pass through the lungs along with the blood and regularly spread to all organs. When administered intraperitoneally, they are absorbed either into the blood or into the lymph and are quickly disseminated throughout the body. The possibility of generalized spread of MSC EVs to distant organs in case of local intratissular administration remains unexplored. However, it is impossible to exclude MSC EV influence on tissues distant from the injection site due to the active or passive migration of these injected nanoparticles through the vessels. The research is based on findings obtained when studying the samples of lungs, heart, spleen, and liver of outbred rabbits of both sexes weighing 3–4 kg at various times after the injection of EVs derived from MSCs of bone marrow origin and labeled by PKH26 into an artificially created defect of the proximal condyle of the tibia. MSC EVs were isolated by serial ultracentrifugation and characterized by transmission electron microscopy and flow cytometry. After the introduction of MSC EVs into the damaged proximal condyle of the tibia of rabbits, these MSC EVs can be found most frequently in the lungs, myocardium, liver, and spleen. MSC EVs enter all of these organs with the blood flow. The lungs contained the maximum number of labeled MSC EVs; moreover, they were often associated with detritus and were located in the lumen of the alveoli. In the capillary network of various organs except the myocardium, MSC EVs are adsorbed by paravasal phagocytes; in some cases, specifically labeled small dust-like objects can be detected throughout the entire experiment—up to ten days of observation. Therefore, we can conclude that the entire body, including distant organs, is effected both by antigenic detritus, which appeared in the bloodstream after extensive surgery, and MSC EVs introduced from the outside.

Author(s):  
Aoyu Zhang ◽  
Bin Liu ◽  
John Liu ◽  
Tianyu Xie

Over the past decade, natural orifice transluminal endoscopic surgery (NOTES) has developed out of a merger of endoscopy and surgery [1]. NOTES offers the advantages of avoiding external incisions and scars, reducing pain, and shortening recovery time by using natural body orifices as the primary portal of entry for surgeries [2]. The NOTES platform consists of a flexible, hollow body — enabling travel in the interior of the human body — and the distal end (head), the mechanical structure of which is based off of the snake bone. After the distal end passes through a natural orifice, through a transluminal opening of the stomach, vagina, bladder, or colon, and reaches the target working place in the peritoneal cavity, several therapeutic and imaging tools can be passed through the hollow conduit of the NOTES’ body for surgeries [3]. The traditional snake bone design presents two major problems. First, the movement is constrained to two bending degrees-of-freedom (DOF). A need to reorient the tool then often requires the entire body to be rotated by the physician, an unwieldly manipulation that both hinders convenience and results in imprecise control. Second, the traditional fabrication process is tedious and therefore lends to higher manufacturing costs; the bending joints must be first individually machined then assembled together piece-by-piece using rotation pins. We propose a novel design for the snake bone that introduces an additional DOF via rotation and is simple and cost-effective to machine. The revised snake bone design features rotation segments controlled by wires that a physician can readily manipulate for increased control and convenience. Further, because surgical tools that pass through the NOTES body conduit are also installed on snake bone structures, the introduction of rotation to the snake bone design increases each tool’s mobility and manipulation. This advance therefore presents the potential to decrease both the number of required tools and the overall diameter of the NOTES body. Finally, the body is machined as a single element and therefore minimizes the work of assembly.


Author(s):  
C.D. Fermin ◽  
M. Igarashi

Otoconia are microscopic geometric structures that cover the sensory epithelia of the utricle and saccule (gravitational receptors) of mammals, and the lagena macula of birds. The importance of otoconia for maintanance of the body balance is evidenced by the abnormal behavior of species with genetic defects of otolith. Although a few reports have dealt with otoconia formation, some basic questions remain unanswered. The chick embryo is desirable for studying otoconial formation because its inner ear structures are easily accessible, and its gestational period is short (21 days of incubation).The results described here are part of an intensive study intended to examine the morphogenesis of the otoconia in the chick embryo (Gallus- domesticus) inner ear. We used chick embryos from the 4th day of incubation until hatching, and examined the specimens with light (LM) and transmission electron microscopy (TEM). The embryos were decapitated, and fixed by immersion with 3% cold glutaraldehyde. The ears and their parts were dissected out under the microscope; no decalcification was used. For LM, the ears were embedded in JB-4 plastic, cut serially at 5 micra and stained with 0.2% toluidine blue and 0.1% basic fuchsin in 25% alcohol.


Author(s):  
P. Fraundorf ◽  
J. Tentschert

Since the discovery of their etchability in the early 1960‘s, nuclear particle tracks in insulators have had a diverse and exciting history of application to problems ranging from the selective filtration of cancer cells from blood to the detection of 244Pu in the early solar system. Their usefulness stems from the fact that they are comprised of a very thin (e.g. 20-40Å) damage core which etches more rapidly than does the bulk material. In fact, because in many insulators tracks are subject to radiolysis damage (beam annealing) in the transmission electron microscope, the body of knowledge concerning etched tracks far outweighs that associated with latent (unetched) tracks in the transmission electron microscope.With the development of scanned probe microscopies with lateral resolutions on the near atomic scale, a closer look at the structure of unetched nuclear particle tracks, particularly at their point of interface with solid surfaces, is now warranted and we think possible. The ion explosion spike model of track formation, described loosely, suggests that a burst of ionization along the path of a charged particle in an insulator creates an electrostatically unstable array of adjacent ions which eject one another by Coulomb repulsion from substitutional into interstitial sites. Regardless of the mechanism, the ejection process which acts to displace atoms along the track core seems likely to operate at track entry and exit surfaces, with the added feature of mass loss at those surfaces as well. In other words, we predict pits whose size is comparable to the track core width.


Author(s):  
H.J. Ryu ◽  
A.B. Shah ◽  
Y. Wang ◽  
W.-H. Chuang ◽  
T. Tong

Abstract When failure analysis is performed on a circuit composed of FinFETs, the degree of defect isolation, in some cases, requires isolation to the fin level inside the problematic FinFET for complete understanding of root cause. This work shows successful application of electron beam alteration of current flow combined with nanoprobing for precise isolation of a defect down to fin level. To understand the mechanism of the leakage, transmission electron microscopy (TEM) slice was made along the leaky drain contact (perpendicular to fin direction) by focused ion beam thinning and lift-out. TEM image shows contact and fin. Stacking fault was found in the body of the silicon fin highlighted by the technique described in this paper.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A737-A737
Author(s):  
Loise Francisco-Anderson ◽  
Loise Francisco-Anderson ◽  
Mary Abdou ◽  
Michael Goldberg ◽  
Erin Troy ◽  
...  

BackgroundThe small intestinal axis (SINTAX) is a network of anatomic and functional connections between the small intestine and the rest of the body. It acts as an immunosurveillance system, integrating signals from the environment that affect physiological processes throughout the body. The impact of events in the gut in the control of tumor immunity is beginning to be appreciated. We have previously shown that an orally delivered single strain of commensal bacteria induces anti-tumor immunity preclinically via pattern recognition receptor-mediated activation of innate and adaptive immunity. Some bacteria produce extracellular vesicles (EVs) that share molecular content with the parent bacterium in a particle that is roughly 1/1000th the volume in a non-replicating form. We report here an orally-delivered and gut-restricted bacterial EV which potently attenuates tumor growth to a greater extent than whole bacteria or checkpoint inhibition.MethodsEDP1908 is a preparation of extracellular vesicles produced by a gram-stain negative strain of bacterium of the Oscillospiraceae family isolated from a human donor. EDP1908 was selected for its immunostimulatory profile in a screen of EVs from a range of distinct microbial strains. Its mechanism of action was determined by ex vivo analysis of the tumor microenvironment (TME) and by in vitro functional studies with murine and human cells.ResultsOral treatment of tumor-bearing mice with EDP1908 shows superior control of tumor growth compared to checkpoint inhibition (anti-PD-1) or an intact microbe. EDP1908 significantly increased the percentage of IFNγ and TNF producing CD8+ CTLs, NK cells, NKT cells and CD4+ cells in the tumor microenvironment (TME). EDP1908 also increased tumor-infiltrating dendritic cells (DC1 and DC2). Analysis of cytokines in the TME showed significant increases in IP-10 and IFNg production in mice treated with EDP1908, creating an environment conducive to the recruitment and activation of anti-tumor lymphocytes.ConclusionsThis is the first report of striking anti-tumor effects of an orally delivered microbial extracellular vesicle. These data point to oral EVs as a new class of immunotherapeutic drugs. They are particularly effective at harnessing the biology of the small intestinal axis, acting locally on host cells in the gut to control distal immune responses within the TME. EDP1908 is in preclinical development for the treatment of cancer.Ethics ApprovalPreclinical murine studies were conducted under the approval of the Avastus Preclinical Services’ Ethics Board. Human in vitro samples were attained by approval of the IntegReview Ethics Board; informed consent was obtained from all subjects.


Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1445
Author(s):  
Taisa Nogueira Pansani ◽  
Thanh Huyen Phan ◽  
Qingyu Lei ◽  
Alexey Kondyurin ◽  
Bill Kalionis ◽  
...  

Extracellular vesicles (EVs) are nanoparticles released by cells that contain a multitude of biomolecules, which act synergistically to signal multiple cell types. EVs are ideal candidates for promoting tissue growth and regeneration. The tissue regenerative potential of EVs raises the tantalizing possibility that immobilizing EVs on implant surfaces could potentially generate highly bioactive and cell-instructive surfaces that would enhance implant integration into the body. Such surfaces could address a critical limitation of current implants, which do not promote bone tissue formation or bond bone. Here, we developed bioactive titanium surface coatings (SurfEV) using two types of EVs: secreted by decidual mesenchymal stem cells (DEVs) and isolated from fermented papaya fluid (PEVs). For each EV type, we determined the size, morphology, and molecular composition. High concentrations of DEVs enhanced cell proliferation, wound closure, and migration distance of osteoblasts. In contrast, the cell proliferation and wound closure decreased with increasing concentration of PEVs. DEVs enhanced Ca/P deposition on the titanium surface, which suggests improvement in bone bonding ability of the implant (i.e., osteointegration). EVs also increased production of Ca and P by osteoblasts and promoted the deposition of mineral phase, which suggests EVs play key roles in cell mineralization. We also found that DEVs stimulated the secretion of secondary EVs observed by the presence of protruding structures on the cell membrane. We concluded that, by functionalizing implant surfaces with specialized EVs, we will be able to enhance implant osteointegration by improving hydroxyapatite formation directly at the surface and potentially circumvent aseptic loosening of implants.


Author(s):  
Julian Bibermair ◽  
Andrew N. Ostrovsky ◽  
Andreas Wanninger ◽  
Thomas Schwaha

AbstractBryozoa is a phylum of aquatic, colonial suspension-feeders within the Lophotrochozoa. In the Phylactolaemata embryonic development occurs in an internal brood sac on the body wall accompanied by extraembryonic nutrition. Owing to previous contradictive descriptions, many aspects of their sexual reproduction require restudy. Consequently, this study analyses embryogenesis of the freshwater bryozoan Plumatella casmiana by serial sections, 3D reconstruction and transmission electron microscopy. Early embryos cleave and soon develop into blastulae with a small central cavity. The mesoderm forms by delamination starting from the distal side towards the proximal end. In later embryos two polypides form on the posterior side that ultimately will be covered by a ciliated mantle in the larva. Embryos increase in size during development and form temporary cell contacts to the embryo sac. Mesodermal cells of the embryo sac show signs of transcellular transport indicating that embryos are nourished by transferring nutrients from the maternal coelom towards the brood cavity. This study clarifies several details such as mesoderm formation and the onset of bud development. Embryos are connected to their respective embryo sacs by a variety of temporary cytoplasmic processes formed by both tissues during embryogenesis, including a ‘placental’ ring zone. Although ultrastructural data of these cell contacts are not entirely conclusive about their function, we suggest that embryos absorb nutrients via the entire surface. The close opposition of embryos to the embryo sac implies placentation as matrotrophic mode in phylactolaemate bryozoans, with embryo sacs acting as placental analogues.


Parasitology ◽  
1971 ◽  
Vol 62 (3) ◽  
pp. 479-488 ◽  
Author(s):  
Gwendolen Rees

Scanning electron-micrographs have shown the covering of microvilli on the surface of the redia of Parorchis acanthus. In the contracted state the elongated microvilli with bulbous extremities seen in the surface grooves may be the result of compression. The surface of the epidermis of the cercaria is smooth on a large area of the ventral surface and lattice-like with microvilli, laterally, anteriorly, dorsally and on the tail. The spines on the body can be withdrawn into sheaths by the contraction of muscle fibres inserted into the basement lamina below each spine.I would like to express my sincere gratitude to Dr I. ap Gwynn of this department for preparing the scanning electron-micrographs and the School of Engineering Science, University of North Wales, Bangor for the use of their stereoscan. I should also like to thank Mr M. C. Bibby for technical assistance and Professor E. G. Gray and Dr W. Sinclair for assistance with the transmission electron-micrographs.


1998 ◽  
Vol 72 (3) ◽  
pp. 215-219 ◽  
Author(s):  
Ho-Choon Woo ◽  
Myung-Deuk Seo ◽  
Sung-Jong Hong

AbstractCentrocestus armatus (Trematoda: Heterophyidae) develops rapidly and produces eggs at 3 days postinfection in albino rats. Excysted metacercariae are pear-shaped and concave ventrally, with 42–44 peg-like circumoral spines. The entire body surface is densely covered with scale-like serrated spines. On juveniles, serration of the tegumental spines is greatest in the middle of the ventral and dorsal surfaces, and decreases anteriorly and posteriorly. Ciliated sensory papillae are concentrated around the oral sucker. Several nonciliated sensory papillae (type II papillae) occur equidistantly on the acetabulum and are arranged in a linear symmetry on the dorsal surface. On adults, the serration of the tegumental spines decreases to 14–17 tips on the ventrolateral surface. The high density of tegumental spines on posterior half of the body and the distribution of type II papillae on dorsal surface are considered to be characteristic of C. armatus.


2003 ◽  
Vol 9 (7) ◽  
pp. 791-804 ◽  
Author(s):  
John Dzielski ◽  
Andrew Kurdila

At very high speeds, underwater bodies develop cavitation bubbles at the trailing edges of sharp corners or from contours where adverse pressure gradients are sufficient to induce flow separation. Coupled with a properly designed cavitator at the nose of a vehicle, this natural cavitation can be augmented with gas to induce a cavity to cover nearly the entire body of the vehicle. The formation of the cavity results in a significant reduction in drag on the vehicle and these so-called high-speed supercavitating vehicles (HSSVs) naturally operate at speeds in excess of 75 m s-1. The first part of this paper presents a derivation of a benchmark problem for control of HSSVs. The benchmark problem focuses exclusively on the pitch-plane dynamics of the body which currently appear to present the most severe challenges. A vehicle model is parametrized in terms of generic parameters of body radius, body length, and body density relative to the surrounding fluid. The forebody shape is assumed to be a right cylindrical cone and the aft two-thirds is assumed to be cylindrical. This effectively parametrizes the inertia characteristics of the body. Assuming the cavitator is a flat plate, control surface lift curves are specified relative to the cavitator effectiveness. A force model for a planing afterbody is also presented. The resulting model is generally unstable whenever in contact with the cavity and stable otherwise, provided the fin effectiveness is large enough. If it is assumed that a cavity separation sensor is not available or that the entire weight of the body is not to be carried on control surfaces, limit cycle oscillations generally result. The weight of the body inevitably forces the vehicle into contact with the cavity and the unstable mode; the body effectively skips on the cavity wall. The general motion can be characterized by switching between two nominally linear models and an external constant forcing function. Because of the extremely short duration of the cavity contact, direct suppression of the oscillations and stable planing appear to present severe challenges to the actuator designer. These challenges are investigated in the second half of the paper, along with several approaches to the design of active control systems.


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