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At least 91 records · Page 5

Comparison of the Effects of Carbon Ion and Photon Irradiation on the Angiogenic Response in Human Lung Adenocarcinoma Cells

Purpose: Radiotherapy resistance is a commonly encountered problem in cancer treatment. In this regard, stabilization of endothelial cells and release of angiogenic factors by cancer cells contribute to this problem. In this study, we used human lung adenocarcinoma (A549) cells to compare the effects of carbon ion and X-ray irradiation on the cells' angiogenic response. Methods and Materials: A549 cells were irradiated with biologically equivalent doses for cell survival of either carbon ions (linear energy transfer, 170 keV/{mu}m; energy of 9.8 MeV/u on target) or X-rays and injected with basement membrane matrix into BALB/c nu/nu mice to generate a plug, allowing quantification of angiogenesis by blood vessel enumeration. The expression of angiogenic factors (VEGF, PlGF, SDF-1, and SCF) was assessed at the mRNA and secreted protein levels by using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay. Signal transduction mediated by stem cell factor (SCF) was assessed by phosphorylation of its receptor c-Kit. For inhibition of SCF/c-Kit signaling, a specific SCF/c-Kit inhibitor (ISCK03) was used. Results: Irradiation of A549 cells with X-rays (6 Gy) but not carbon ions (2 Gy) resulted in a significant increase in blood vessel density (control, 20.71 {+-} 1.55; X-ray, 36.44 {+-} 3.44; carbon ion, 16.33 {+-} 1.03; number per microscopic field). Concordantly, irradiation with X-rays but not with carbon ions increased the expression of SCF and subsequently caused phosphorylation of c-Kit in endothelial cells. ISCK03 treatment of A549 cells irradiated with X-rays (6 Gy) resulted in a significant decrease in blood vessel density (X-ray, 36.44 {+-} 3.44; X-ray and ISCK03, 4.33 {+-} 0.71; number of microscopic field). These data indicate that irradiation of A549 cells with X-rays but not with carbon ions promotes angiogenesis. Conclusions: The present study provides evidence that SCF is an X-ray-induced mediator of angiogenesis in A549 cells, a phenomenon that could not be observed with carbon ion irradiation. Thus, in this model system evaluating angiogenesis, carbon ion irradiation may have a therapeutic advantage. This observation should be confirmed in orthotopic lung tumor models.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Serotonin, atherosclerosis, and collateral vessel spasm

Studies on animal models demonstrate that platelet products contribute to vascular spasm in ischemic syndromes and that this is reversible with administration of ketanserin and thromboxane synthesis inhibitors. Laboratory animals (dogs, rabbits, and rats) that had femoral artery ligations exhibited supersensitivity to serotonin within days in their collateral blood vessels. This supersensitivity lasted at least 6 months. The response to serotonin was reversed by ketanserin, but not by 5HT-1 antagonists. Supersensitivity does not extend to norepinephrine, and alpha blockers do not influence the response to serotonin. It appears that platelet activation by endothelial injury contributes to ischemia through blood vessel occlusion and vascular spasm. When platelet activation occurs in vivo, blood vessel occlusion and vascular spasm are reversible in part by using ketanserin or agents that block thromboxane synthesis or its action. Combining both classes of agents reverses spasm completely. These findings support existing evidence that platelet products contribute to vascular disease, and provide an approach to improved management with currently available pharmacologic agents.

Review, Tutorial↗

Luminal surface fabrication for cardiovascular prostheses

A method is provided for forming a mold surface with microscopic upstanding pillars for molding the inside surface of a vascular prostheses (synthetic blood vessel). The mold article is formed from a quantity of Teflon (polytetrafluoroethylene) which has a polished, flat surface on which a gold film has been sputter deposited. A photoresist layer, which cannot adhere directly to Teflon, adheres to the gold. The photoresist is exposed and developed leaving a sputter resistant mask defining the desired pillar locations, and the resulting workpiece is ion etched to form the pillars in the Teflon. A synthetic blood vessel material is cast against the Teflon mold to form blind recesses on the inside of the synthetic blood vessel, with the recesses being of predetermined uniform cross section and present in a predetermined uniform pattern.

Deininger, William D.↗

VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation

In ischemic disorders such as chronic wounds and myocardial ischemia, there is inadequate tissue perfusion due to vascular insufficiency. Besides, it has been observed that prolonged use of anti-angiogenic agents in cancer therapy produces cardiovascular toxicity caused by impaired vessel integrity and regeneration. In the present study, we used VEGFR tyrosine kinase inhibitor II (VRI) to chemically induce vascular insufficiency in zebrafish in vivo and human umbilical vein endothelial cells (HUVEC) in vitro to further study the mechanisms of vascular morphogenesis in these pathological conditions. We also explored the possibility of treating vascular insufficiency by enhancing vascular regeneration and repair with pharmacological intervention. We observed that pretreatment of VRI induced blood vessel loss in developing zebrafish by inhibiting angiogenesis and increasing endothelial cell apoptosis, accompanied by down-regulation of kdr, kdrl and flt-1 genes expression. The VRI-induced blood vessel loss in zebrafish could be restored by post-treatment of calycosin, a cardiovascular protective isoflavone. Similarly, VRI induced cytotoxicity and apoptosis in HUVEC which could be rescued by calycosin post-treatment. Further investigation of the underlying mechanisms showed that the PI3K/AKT/Bad cell survival pathway was a main contributor of the vascular regenerative effect of calycosin. These findings indicated that the cardiovascular toxicity in anti-angiogenic therapy was mainly caused by insufficient endothelial cell survival, suggesting its essential role in vascular integrity, repair and regeneration. In addition, we showed that VRI-induced blood vessel loss in zebrafish represented a simple and effective in vivo model for studying vascular insufficiency and evaluating cancer drug vascular toxicities. - Highlights: • In vivo VRI model • Rescue effects of calycosin • Calycosin EC survival pathways.

60 APPLIED LIFE SCIENCES↗

The role of vascular niche and endothelial cells in organogenesis and regeneration

Highlights: • The vascular niche creates a permissive environment that realize developmental or regenerative programs. • The proximity between endothelium and cells of organs suggests a role of endothelial cells in the organs maturation. • Organs provide cues shaping vascular network structure. The term vascular niche indicate the physical and biochemical microenvironment around blood vessel where endothelial cells, pericytes, and smooth muscle cells organize themselves to form blood vessels and release molecules involved in the recruitment of hematopoietic stem cells, endothelial progenitor cells and mesenchymal stem cells. The vascular niche creates a permissive environment that enables different cell types to realize their developmental or regenerative programs. In this context, the proximity between the endothelium and the new-forming cellular components of organs suggests an essential role of endothelial cells in the organs maturation. Dynamic interactions between specific organ endothelial cells and different cellular conponents are crucial for different organ morphogenesis and function. Conversely, organs provide cues shaping vascular network structure.

60 APPLIED LIFE SCIENCES↗

Poster — Thur Eve — 70: Automatic lung bronchial and vessel bifurcations detection algorithm for deformable image registration assessment

Purpose: To investigate an automatic bronchial and vessel bifurcations detection algorithm for deformable image registration (DIR) assessment to improve lung cancer radiation treatment. Methods: 4DCT datasets were acquired and exported to Varian treatment planning system (TPS) EclipseTM for contouring. The lungs TPS contour was used as the prior shape for a segmentation algorithm based on hierarchical surface deformation that identifies the deformed lungs volumes of the 10 breathing phases. Hounsfield unit (HU) threshold filter was applied within the segmented lung volumes to identify blood vessels and airways. Segmented blood vessels and airways were skeletonised using a hierarchical curve-skeleton algorithm based on a generalized potential field approach. A graph representation of the computed skeleton was generated to assign one of three labels to each node: the termination node, the continuation node or the branching node. Results: 320 ± 51 bifurcations were detected in the right lung of a patient for the 10 breathing phases. The bifurcations were visually analyzed. 92 ± 10 bifurcations were found in the upper half of the lung and 228 ± 45 bifurcations were found in the lower half of the lung. Discrepancies between ten vessel trees were mainly ascribed to large deformation and in regions where the HU varies. Conclusions: We established an automatic method for DIR assessment using the morphological information of the patient anatomy. This approach allows a description of the lung's internal structure movement, which is needed to validate the DIR deformation fields for accurate 4D cancer treatment planning.

60 APPLIED LIFE SCIENCES↗

Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury

Curculigoside A has shown protective effects against rat cortical neuron damage in vivo. However, the molecular mechanisms through which Curculigoside A affords this protection are unclear. In the present study, we sought to elucidate the mechanisms of angiogenesis in rat aortic endothelial cells (RAEC), rat aortic smooth muscle cells (RASMC) as well as a rat model of cerebral ischemia and reperfusion injury following treatment with Curculigoside A. We examined the role of Curculigoside A on RAEC and RASMC proliferation, migration, and tube formation in vitro and in a cerebral ischemia and reperfusion injury rat model. We used the recombinant Dickkopf (DKK)-1 protein, a Wnt/β-catenin inhibitor, and the recombinant WIF-1 protein, a Wnt5a antagonist to determine mechanisms. In addition, we measured leakage of the blood–brain barrier (BBB) and tested for angiogenesis associated proteins. Our data suggest that Curculigoside A induces angiogenesis in vitro by increasing proliferation, migration and tube formation in RAEC and RASMC. The increase in Curculigoside A-induced proliferation and tube formation was counteracted by DKK-1 and WIF-1. Curculigoside A increased expression of VEGF, p-VEGFR, p-CREB, Egr-3, VCAM-1, Ang1 and Tie2 while prohibiting BBB leakage in cerebral ischemia and reperfusion injured rats. However, Cyclosporine A, a CREB inhibitor, reduced the expression of p-CREB, Egr-3, VCAM-1, Ang1 and Tie2. These data suggest that Curculigoside A induces cell proliferation and angiogenesis through the Wnt5a/β-catenin and VEGF/CREB/Egr-3/VCAM-1 signaling axis and promotes maturation and stability of new blood vessels via increasing Ang1 and Tie-2 expression. - Highlights: • Curculigoside A induces cell proliferation through Wnt5a/β-catenin pathway. • Curculigoside A induces angiogenesis via VEGF/CREB/Egr-3/VCAM-1 signaling axis. • Curculigoside A promotes blood vessel maturation via Ang1/Tie2 pathway.

60 APPLIED LIFE SCIENCES↗

Neutrophils infiltrating pancreatic ductal adenocarcinoma indicate higher malignancy and worse prognosis

Highlights: • Previous studies have reported that inflammation and peroxides may promote development of pancreatic ductal adenocarcinoma (PDAC). • Neutrophils, as inflammatory cells, can produce or peroxides in the stroma of cancer. . • It is difficult to investigate the interaction between neutrophils and PDAC cells. Here, CD177 was used to show distribution of neutrophils. • Expression of CD177 was negatively correlated with overall survival of patients. This phenomenon was observed from pathological specimens. • Therefore, we speculate that neutrophils infiltration is a negative prognostic factor for PDAC. CD177 is considered to represent neutrophils. We analyzed mRNA expression level of CD177 and clinical follow-up survey of PDAC to estimate overall survival (OS) from Gene Expression Omnibus (GEO) dataset (GSE21501, containing samples from 102 PDAC patients) by R2 platform (http://r2.amc.nl). We also analyzed correlated genes of CD177 by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to predict the potential relationship between neutrophils and prognosis of PDAC. We then performed hematoxylin and eosin (H&E) staining and immunohistochemical staining of surgical specimens to verify infiltration of neutrophils in PDAC tissues. After analyzing mRNA expression data and clinical follow-up survey provided in the GEO dataset (GSE21501, containing samples from 102 PDAC patients) and clinicopathological data of 23 PDAC patients, we demonstrated that CD177 was correlated with poor prognosis. The univariate Kaplan–Meier survival analysis revealed that OS was inversely associated with increased expression of CD177 (P = 0.012). Expression of phosphodiesterase (PDE)4D was positively related to CD177 in gene correlation analysis (R = 0.413, P < 0.001) by R2 platform. H&E staining and immunohistochemistry of CD177 in 23 PDAC surgical samples showed accumulation of neutrophils in the stroma and blood vessels around the cancer cells. In addition, immunohistochemical staining showed that CD177 was highly expressed in the stroma and blood vessels around tumor tissues of PDAC, which was similar to H&E staining. Expression of CD177 can be used to represent infiltration of neutrophils, which may have potential prognostic value in PDAC.

60 APPLIED LIFE SCIENCES↗

Deep Learning Approaches to Surrogates for Solving the Diffusion Equation for Mechanistic Real-World Simulations

In many mechanistic medical, biological, physical, and engineered spatiotemporal dynamic models the numerical solution of partial differential equations (PDEs), especially for diffusion, fluid flow and mechanical relaxation, can make simulations impractically slow. Biological models of tissues and organs often require the simultaneous calculation of the spatial variation of concentration of dozens of diffusing chemical species. One clinical example where rapid calculation of a diffusing field is of use is the estimation of oxygen gradients in the retina, based on imaging of the retinal vasculature, to guide surgical interventions in diabetic retinopathy. Furthermore, the ability to predict blood perfusion and oxygenation may one day guide clinical interventions in diverse settings, i.e., from stent placement in treating heart disease to BOLD fMRI interpretation in evaluating cognitive function (Xie et al., 2019; Lee et al., 2020). Since the quasi-steady-state solutions required for fast-diffusing chemical species like oxygen are particularly computationally costly, we consider the use of a neural network to provide an approximate solution to the steady-state diffusion equation. Machine learning surrogates, neural networks trained to provide approximate solutions to such complicated numerical problems, can often provide speed-ups of several orders of magnitude compared to direct calculation. Surrogates of PDEs could enable use of larger and more detailed models than are possible with direct calculation and can make including such simulations in real-time or near-real time workflows practical. Creating a surrogate requires running the direct calculation tens of thousands of times to generate training data and then training the neural network, both of which are computationally expensive. Often the practical applications of such models require thousands to millions of replica simulations, for example for parameter identification and uncertainty quantification, each of which gains speed from surrogate use and rapidly recovers the up-front costs of surrogate generation. We use a Convolutional Neural Network to approximate the stationary solution to the diffusion equation in the case of two equal-diameter, circular, constant-value sources located at random positions in a two-dimensional square domain with absorbing boundary conditions. Such a configuration caricatures the chemical concentration field of a fast-diffusing species like oxygen in a tissue with two parallel blood vessels in a cross section perpendicular to the two blood vessels. To improve convergence during training, we apply a training approach that uses roll-back to reject stochastic changes to the network that increase the loss function. The trained neural network approximation is about 1000 times faster than the direct calculation for individual replicas. Because different applications will have different criteria for acceptable approximation accuracy, we discuss a variety of loss functions and accuracy estimators that can help select the best network for a particular application. We briefly discuss some of the issues we encountered with overfitting, mismapping of the field values and the geometrical conditions that lead to large absolute and relative errors in the approximate solution.

60 APPLIED LIFE SCIENCES↗

Irreversible Electroporation in a Swine Lung Model

Purpose: This study was designed to evaluate the safety and tissue effects of IRE in a swine lung model. Methods: This study was approved by the institutional animal care committee. Nine anesthetized domestic swine underwent 15 percutaneous irreversible electroporation (IRE) lesion creations (6 with bipolar and 3 with 3-4 monopolar electrodes) under fluoroscopic guidance and with pancuronium neuromuscular blockade and EKG gating. IRE electrodes were placed into the central and middle third of the right mid and lower lobes in all animals. Postprocedure PA and lateral chest radiographs were obtained to evaluate for pneumothorax. Three animals were sacrificed at 2 weeks and six at 4 weeks. Animals underwent high-resolution CT scanning and PA and lateral radiographs 1 h before sacrifice. The treated lungs were removed en bloc, perfused with formalin, and sectioned. Gross pathologic and microscopic changes after standard hematoxylin and eosin staining were analyzed within the areas of IRE lesion creation. Results: No significant adverse events were identified. CT showed focal areas of spiculated high density ranging in greatest diameter from 1.1-2.2 cm. On gross inspection of the sectioned lung, focal areas of tan discoloration and increased density were palpated in the areas of IRE. Histological analysis revealed focal areas of diffuse alveolar damage with fibrosis and inflammatory infiltration that respected the boundaries of the interlobular septae. No pathological difference could be discerned between the 2- and 4-week time points. The bronchioles and blood vessels within the areas of IRE were intact and did not show signs of tissue injury. Conclusion: IRE creates focal areas of diffuse alveolar damage without creating damage to the bronchioles or blood vessels. Short-term safety in a swine model appears to be satisfactory.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

NASA Robotic Neurosurgery Testbed

The detection of tissue interface (e.g., normal tissue, cancer, tumor) has been limited clinically to tactile feedback, temperature monitoring, and the use of a miniature ultrasound probe for tissue differentiation during surgical operations. In neurosurgery, the needle used in the standard stereotactic CT (Computational Tomography) or MRI (Magnetic Resonance Imaging) guided brain biopsy provides no information about the tissue being sampled. The tissue sampled depends entirely upon the accuracy with which the localization provided by the preoperative CT or MRI scan is translated to the intracranial biopsy site. In addition, no information about the tissue being traversed by the needle (e.g., a blood vessel) is provided. Hemorrhage due to the biopsy needle tearing a blood vessel within the brain is the most devastating complication of stereotactic CT/MRI guided brain biopsy. A robotic neurosurgery testbed has been developed at NASA Ames Research Center as a spin-off of technologies from space, aeronautics and medical programs. The invention entitled 'Robotic Neurosurgery Leading to Multimodality Devices for Tissue Identification' is nearing a state ready for commercialization. The devices will: 1) improve diagnostic accuracy and precision of general surgery, with near term emphasis on stereotactic brain biopsy, 2) automate tissue identification, with near term emphasis on stereotactic brain biopsy, to permit remote control of the procedure, and 3) reduce morbidity for stereotactic brain biopsy. The commercial impact from this work is the potential development of a whole new generation of smart surgical tools to increase the safety, accuracy and efficiency of surgical procedures. Other potential markets include smart surgical tools for tumor ablation in neurosurgery, general exploratory surgery, prostate cancer surgery, and breast cancer surgery.

Mah, Robert↗

NASA Robotic Neurosurgery Testbed

The detection of tissue interface (e.g., normal tissue, cancer, tumor) has been limited clinically to tactile feedback, temperature monitoring, and the use of a miniature ultrasound probe for tissue differentiation during surgical operations, In neurosurgery, the needle used in the standard stereotactic CT or MRI guided brain biopsy provides no information about the tissue being sampled. The tissue sampled depends entirely upon the accuracy with which the localization provided by the preoperative CT or MRI scan is translated to the intracranial biopsy site. In addition, no information about the tissue being traversed by the needle (e.g., a blood vessel) is provided. Hemorrhage due to the biopsy needle tearing a blood vessel within the brain is the most devastating complication of stereotactic CT/MRI guided brain biopsy. A robotic neurosurgery testbed has been developed at NASA Ames Research Center as a spin-off of technologies from space, aeronautics and medical programs. The invention entitled "Robotic Neurosurgery Leading to Multimodality Devices for Tissue Identification" is nearing a state ready for commercialization. The devices will: 1) improve diagnostic accuracy and precision of general surgery, with near term emphasis on stereotactic brain biopsy, 2) automate tissue identification, with near term emphasis on stereotactic brain biopsy, to permit remote control of the procedure, and 3) reduce morbidity for stereotactic brain biopsy. The commercial impact from this work is the potential development of a whole new generation of smart surgical tools to increase the safety, accuracy and efficiency of surgical procedures. Other potential markets include smart surgical tools for tumor ablation in neurosurgery, general exploratory surgery, prostate cancer surgery, and breast cancer surgery.

Mah, Robert↗

Effect of gravitational overloads, hypokinesia and hypodynamia on the vessels of the pulmonary blood circuit

Vessels of the pulmonary circuit are studied under normal conditions, in exposure to single stress or continuous threshold endurable chestspine gravitational stresses, and one to eight weak hypokinesia and hypodynamic effects followed by stress. Examination methods include rentgenography and microrentgenography, clearing, and histology. In exposure to gravitational stress the distal portions of the arterial vessels of the 3 and 4 orders constrict, while all veins dilate. Sinuosity of all vessels is noted. The volume of the capillary bed increases and signs of perivascular edema occur. Due to hypokinesia and hypodynamia the arteries constricted and the arterial bed becomes poor. The veins of all orders dilate and the volume of the capillary bed increases. The changes grew greater the longer the terms of hypodyamic effects. Successive combination of hypokinesia and hypodynamia and gravitational stresses cause more pronounced changes than separate effects of these two factors and result in great deformity of the vascular walls, including their rupture and penetration of formed elements beyond the limits of the vascular bed.

Kasimtsev, A. A.↗

Differences in Pre and Post Vascular Patterning Within Retinas from ISS Crew Members and Head-Down Tilt (HDT) Subjects by VESGEN Analysis

Accelerated research by NASA has investigated the significant risks incurred during long-duration missions in microgravity for Space Flight-Associated Neuro-ocular Syndrome (SANS, formerly known as Visual Impairments associated with Increased Intracranial Pressure, VIIP) [1]. For our study, NASA's VESsel GENeration Analysis (VESGEN) was used to investigate the role of retinal blood vessels in the etiology of SANS/VIIP. The response of retinal vessels to microgravity was evaluated in astronaut crew members pre and post flight to the International Space Station (ISS), and compared to the response of retinal vessels in healthy volunteers to 6deg head-down tilt during 70 days of bed rest (HDTBR). For the study, we are testing the hypothesis that long-term cephalad fluid shifts resulting in ocular and visual impairments are necessarily mediated in part by retinal blood vessels, and therefore are accompanied by structural adaptations of the vessels. METHODS: Vascular patterns in the retinas of crew members and HDTBR subjects extracted from 30deg infrared (IR) Heidelberg Spectralis images collected pre/postflight and pre/post HDTBR, respectively, were analyzed by VESGEN (patent pending). VESGEN is a mature, automated software developed as a research discovery tool for progressive vascular diseases in the retina and other tissues. The multi-parametric VESGEN analysis generates maps of branching arterial and venous trees quantified by parameters such as the fractal dimension (Df, a modern measure of vascular space-filling capacity), vessel diameters, and densities of vessel length and number classified into specific branching generations according to vascular physiological branching rules. The retrospective study approved by NASA's Institutional Review Board included the analysis of bilateral retinas in eight ISS crew members monitored by routine occupational surveillance and six HDTBR subjects (NASA FARU Campaign 11, for example). The VESGEN analysis was conducted in a blinded fashion, with IR retinal images masked to the subject's identity, ophthalmic and clinical characteristics, and to the temporal sequence of image collection. To complete our study, VESGEN results will be analyzed statistically and correlated with other ophthalmic and medical findings. RESULTS: Preliminary results for changes in the pre to post status of vascular patterning in the retinas of crew members and HDTBR subjects are interestingly opposite. By Df and other vascular branching measures, the space-filling capacity of arterial and venous trees decreased in the majority of crew members (11/16 retinas). In contrast, vascular densities increased in HDTBR subjects by the same parameters (6/10 retinas). To conclude the study, biostatistics and medical analyses will be conducted to quantify and draw conclusions about how the changes associated with flight compare to those associated with HDTBR. CONCLUSIONS: Vascular densities appeared to decrease in the retinas of ISS crew members and increase in HDTBR subjects. Differences in arterial and venous response to cephalad fluid shifts induced by ISS and HDTBR may have resulted from a long-duration conditioning phenomenon (for example, 6-month ISS missions compared to 70 days HDTBR), or the presence of gravity in HDTBR compared to microgravity on the ISS. In addition, increased and decreased vessel diameters for Crew Members and HDTBR, respectively, are subject to limits of im

Vascular↗

Visualisation of distribution of gold nanoparticles in liver tissues ex vivo and in vitro using the method of optical coherence tomography

The possibility of visualising the distribution of gold nanoparticles in liver by means of the method of optical coherence tomography is studied experimentally in model samples of beef liver in vitro and rat liver ex vivo. In the experiments we used the gold nanoparticles in the form of nanocages with resonance absorption in the near-IR spectral region. In the model studies the suspension of nanoparticles was applied to the surface of the sample, which then was treated with ultrasound. In the ex vivo studies the suspension of nanoparticles was injected to the laboratory rats intravenously. The image contrast and the optical depth of detection of blood vessels and liver structure components are calculated, as well as the depth of liver optical probing before and after the injection of nanoparticles. It was shown that the administration of the nanoparticle increases significantly the imaging contrast of liver blood vessels owing to the localisation of the nanoparticles therein.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Raster scanning and averaging for reducing the influence of speckles in optical coherence tomography

The application of small-angle raster scanning and averaging in the sample arm of the Michelson interferometer in optical coherence tomography (OCT) is described. Raster averaging is used to increase the signal-to-noise ratio and to reduce the speckle noise of the 2D OCT image in diagnostics of surface layers of human skin and subcutaneous blood vessels in vivo. The method allows using low-coherence source of low-power radiation and increasing the depth of human skin coherent probing up to 1.5 - 1.8 mm. The reduction of speckle noise in the obtained OCT image for the first time allowed visualisation of subcutaneous blood vessels at the entire depth of their localisation. (biophotonics)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Intraperitoneal injection of MSC-derived exosomes prevent experimental bronchopulmonary dysplasia

Mesenchymal stromal cell (MSC) derived exosomes mediate tissue protection and regeneration in many injuries and diseases by modulating cell protein production, protecting from apoptosis, inhibiting inflammation, and increasing angiogenesis. In the present study, daily intraperitoneal injection of MSC-derived exosomes protected alveolarization and angiogenesis in a newborn rat model of bronchopulmonary dysplasia (BPD) induced by 14 days of neonatal hyperoxia exposure (85% O{sub 2}). Exosome treatment during hyperoxia prevented disruption of alveolar growth, increased small blood vessel number, and inhibited right heart hypertrophy at P14, P21, and P56. In vitro, exosomes significantly increased tube-like network formation by HUVEC, in part through a VEGF mediated mechanism. In summary, daily intraperitoneal injection of exosomes increased blood vessel number and size in the lung through pro-angiogenic mechanisms. MSC-derived exosomes therefore have both anti-inflammatory and pro-angiogenic mechanism to protect the lung from hyperoxia induced lung and heart disease associated with BPD.

60 APPLIED LIFE SCIENCES↗

Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing

Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular, the spatial localization of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.

59 BASIC BIOLOGICAL SCIENCES↗