Les encéphalopathies épileptogènes sont des maladies graves de l’enfance associant une épilepsie, souvent réfractaire, et un retard de développement. Les mécanismes sous-tendant ces maladies sont peu connus. Cependant, nous postulons que ces épilepsies puissent être causées par une dysfonction du réseau inhibiteur. En effet, des défauts de migration ou de maturation des interneurones GABAergiques (INs) corticaux induisent l’épilepsie, tant chez l’humain que chez la souris. Dans le but d’étudier les causes génétiques des encéphalopathies épileptogènes sporadiques inexpliquées, le laboratoire de la Dre Rossignol a procédé au séquençage d’exome entier d’une cohorte d’enfants atteints. Cela a permis d’identifier, chez un patient, une nouvelle mutation de novo, possiblement pathogène, dans le gène MYO9b. MYO9b est impliqué dans la migration de cellules immunitaires et cancéreuses et est exprimée durant le développement cérébral. Nous émettons l’hypothèse voulant que MYO9b puisse être importante pour la migration des INs corticaux. Les résultats présentés dans ce mémoire démontrent que Myo9b est exprimé dès le stade embryonnaire par les progéniteurs des INs corticaux et que son expression se restreint aux INs dans le cortex mature. De plus, nous démontrons que la répression ex vivo de Myo9b sélectivement dans les INs au sein de tranches corticales organotypiques embryonnaires mène à des défauts morphologiques majeurs de ces cellules en migration. En effet, ces cellules présentent une morphologie multipolaire et des neurites rostraux plus longs et plus complexes. Ces changements morphologiques pourraient avoir un impact majeur sur la migration des INs et ainsi perturber le développement des réseaux inhibiteurs. / Epileptic encephalopathies are early-onset diseases characterized by refractory epilepsy with developmental delay. To identify the underlying genetic cause of these disorders, Dr Rossignol’s laboratory has performed whole-exome sequencing in children with sporadic epileptic encephalopathies. They have identified a novel de novo mutation in the MYO9B gene in one patient. Myo9b is known to regulate cell migration in the immune system and in cancer cells. It is expressed in the developing rodent brain, but its roles during brain development are largely unknown. Recent evidence suggests that epilepsy can be caused by an imbalance between inhibition and excitation in cortical circuits. Indeed, defects in the development or the functions of cortical GABAergic interneurons (INs) have been associated with epilepsy in human and in mouse models. Therefore, we postulated that Myo9b might play a role in the development of INs. In this thesis, I show that Myo9b is expressed in INs from early embryonic ages to post-natal ages. Furthermore, I demonstrate that the ex vivo downregulation of Myo9b in INs in cortical embryonic organotypic cultures causes morphological defects in migrating INs, including aberrant polarization of these cells. These morphological changes might result in aberrant IN migration, which would be expected to perturb the cortical inhibitory-excitatory ratio.

Dans cette thèse, nous nous intéressons à l’étude des courbes discrètes bruitées qui correspondent aux contours d’objets dans des images. Nous avons proposé plusieurs outils permettant de les analyser. Les points dominants (points dont l’estimation de la courbure est localement maximale) jouent un rôle très important dans la reconnaissance de formes et, nous avons développé une méthode non heuristique, rapide et fiable pour les détecter dans une courbe discrète. Cette méthode est une amélioration d’une méthode existante introduite par Nguyen et al. La nouvelle méthode consiste à calculer une mesure d’angle. Nous avons proposé aussi deux approches pour la simplification polygonale : une méthode automatique minimisant, et une autre fixant le nombre de sommets du polygone résultant. Ensuite, nous avons introduit un nouvel outil géométrique, nommé couverture tangentielle adaptative (ATC), reposant sur la détection des épaisseurs significatives introduites par Kerautret et al. Ces épaisseurs calculées en chaque point du contour à analyser, permettent d’estimer localement le niveau de bruit. Dans ce contexte notre algorithme de construction de la couverture tangentielle adaptative prend en considération les différents niveaux de bruits présents dans la courbe à étudier et ne nécessite pas de paramètre. Deux applications de l’ATC sont proposées en analyse d’images : d’une part la décomposition des contours d’une forme dans une image en arcs et en segments de droite et d’autre part, dans le cadre d’un projet avec une université d’Inde, autour du langage des signes et la reconnaissance des gestes de la main. Premièrement, la méthode de décomposition des courbes discrètes en arcs et en segments de droite est basée sur deux outils : la détection de points dominants en utilisant la couverture tangentielle adaptative et la représentation dans l’espace des tangentes du polygone, issue des points dominants détectés. Les expériences montrent la robustesse de la méthode w.r.t. le bruit. Deuxièmement, à partir des contours des mains extraits d’images prises par une Kinect, nous proposons différents descripteurs reposant sur des points dominants sélectionnés du contour des formes dans les images. Les descripteurs proposés, qui sont une combinaison entre descripteurs statistiques et descripteurs géométriques, sont efficaces et conviennent à la reconnaissance de gestes / In this thesis, we are interested in the study of noisy discrete curves that correspond to the contours of objects in images. We have proposed several tools to analyze them. The dominant points (points whose curvature estimation is locally maximal) play a very important role in pattern recognition and we have developed a non-heuristic, fast and reliable method to detect them in a discrete curve. This method is an improvement of an existing method introduced by Nguyen et al. The new method consists in calculating a measure of angle. We have also proposed two approaches for polygonal simplification: an automatic method minimizing, and another fixing the vertex number of the resulting polygon. Then we proposed a new geometric tool, called adaptive tangential cover ATC, based on the detection of meaningful thickness introduced by Kerautret et al. These thicknesses are calculated at each point of the contours allow to locally estimate the noise level. In this context our construction algorithm of adaptive tangential cover takes into account the different levels of noise present in the curve to be studied and does not require a parameter. Two applications of ATC in image analysis are proposed: on the one hand the decomposition of the contours of a shape in an image into arcs and right segments and on the other hand, within the framework of a project with an Indian university about the sign language and recognition of hand gestures. Firstly, the method to decompose discrete curves into arcs and straight segments is based on two tools: dominant point detection using adaptive tangential cover and tangent space representation of the polygon issued from detected dominant points. The experiments demonstrate the robustness of the method w.r.t. noise. Secondly, from the outlines of the hands extracted from images taken by a Kinect, we propose several descriptors from the selected dominant points computed from the adaptive tangential cover. The proposed descriptors, which are a combination of statistical descriptors and geometrical descriptors, are effective and suitable for gesture recognition

<p>In this thesis we discuss different types of regularity for distributions which appear in the theory of pseudo-differential operators and partial differential equations. Partial differential equations often appear in science and technology. For example the Schrödinger equation can be used to describe the change in time of quantum states of physical systems. Pseudo-differential operators can be used to solve partial differential equations.  They are also appropriate to use when modeling different types of problems within physics and engineering. For example, there is a natural connection between pseudo-differential operators and stationary and non-stationary filters in signal processing. Furthermore, the correspondence between symbols and operators when passing from classical mechanics to quantum mechanics essentially agrees with symbols and operators in the Weyl calculus of pseudo-differential operators.</p><p>In this thesis we concentrate on investigating how regularity properties for solutions of partial differential equations are affected under the mapping of pseudo-differential operators, and in particular of the free time-dependent Schrödinger operators.</p><p>The solution of the free time-dependent Schrödinger equation can be expressed as a pseudo-differential operator, with non-smooth symbol, acting on the initial condition. We generalize a result about non-tangential convergence, which was obtained by Sjögren and Sjölin (1989) for the free time-dependent Schrödinger equation.</p><p>Another way to describe regularity for a distribution is to use wave-front sets. They do not only describe where the singularities are, but also the directions in which these singularities appear. The first types of wave-front sets (analytical wave-front sets) were introduced by Sato (1969, 1970). Later on Hörmander introduced ``classical'' wave-front sets (with respect to smoothness) and showed results in the context of pseudo-differential operators with smooth symbols, cf. Hörmander (1985).</p><p>In this thesis we consider wave-front sets with respect to Fourier Banach function spaces. Roughly speaking, we take <em>B</em> as a Banach space, which is invariant under translations and embedded between the space of Schwartz functions and the space of temperated distributions. Then we say that the wave-front set of a distribution contains all points (x₀, ξ₀) such that no localization of the distribution at x₀, belongs to <em>FB</em> in the direction ξ₀. We prove that pseudo-differential operators with smooth symbols shrink the wave-front set and we obtain opposite embeddings by using sets of characteristic points of the operator symbols.</p> / <p>I denna avhandling diskuterar vi olika typer av regularitet för distributioner som uppkommer i teorin för pseudodifferentialoperatorer och partiella differentialekvationer. Partiella differentialekvationer förekommer inom naturvetenskap och teknik. Exempelvis kan Schrödingerekvationen användas för att beskriva förändringen med tiden av kvanttillstånd i fysikaliska system. Pseudodifferentialoperatorer kan användas för att lösa partiella differential\-ekvationer. De användas också för att modellera olika typer av problem inom fysik och teknik. Det finns till exempel en naturlig koppling mellan pseudodifferentialoperatorer och stationära och icke-stationära filter i signalbehandling. Vidare gäller att relationen mellan symboler och operatorer vid övergången från klassisk mekanik till kvantmekanik i huvudsak överensstämmer med symboler och operatorer inom Weylkalkylen för pseudodifferentialoperatorer.</p><p>I den här avhandlingen koncentrerar vi oss på att undersöka hur regularitetsegenskaper för lösningar till partiella differentialekvationer påverkas under verkan av pseudodifferentialoperatorer, och speciellt för de fria tidsberoende Schrödingeroperatorerna.</p><p>Lösningen av den fria tidsberoende Schrödingerekvationen kan uttryckas som en pseudodifferentialoperator, med icke-slät symbol, verkande på begynnelsevillkoret. Vi generaliserar ett resultat om icke-tangentiell konvergens av Sjögren och Sjölin (1989) för den fria tidsberoende Schrödingerekvationen.</p><p>Ett annat sätt att beskriva regularitet hos en distribution är med hjälp av vågfrontsmängder. De beskriver inte bara var singulariteterna finns, utan också i vilka riktningar dessa singulariteter förekommer. De första typerna av vågfrontsmängder (analytiska vågfrontsmängder) introducerades av Sato (1969, 1970). Senare introducerade Hörmander ''klassiska'' vågfrontsmängder (med avseende på släthet) och visade resultat för verkan av pseudodifferentialoperatorer med släta symboler, se  Hörmander (1985).</p><p>I denna avhandling betraktar vi vågfrontsmängder med avseende på Fourier Banach funktionsrum. Detta kan ses som att vi låter <em>B</em> vara ett Banachrum, som är invariant under translationer och är inbäddat mellan rummet av Schwartzfunktioner och rummet av tempererade distributioner. Vågfrontsmängden av en distribution innehåller alla punkter (x₀, ξ₀) så att ingen lokalisering av distributionen kring x₀, tillhör <em>FB</em> i riktningen ξ₀. Vi visar att pseudodifferentialoperatorer med släta symboler krymper vågfrontsmängden och vi får motsatta inbäddningar med hjälp mängder av karakteristiska punkter till operatorernas symboler.</p>

The aim of this thesis was to investigate roller ski characteristics; classical and freestyle roller skis’ rolling resistance coefficients (μR) and classical style roller skis’ static friction coefficients (μS), and to study the influence of different μR and μS on cross-country skiers’ performance and both physiological and biomechanical indices. The aim was also to study differences in skiing economy and efficiency between recreational skiers, female and male junior and senior elite cross-country skiers.The experiments showed that during a time period of 30 minutes of rolling on a treadmill (warm-up), μR decreased significantly (p&lt;0.05) to about 60-65 % and 70-75 % of its initial value for freestyle and classical roller skis respectively. Also, there was a significant influence of normal force on μR, while different velocities and inclinations of the treadmill only resulted in small changes in μR.The study of the influence on physiological variables of a ~50 % change in μR showed that during submaximal steady rate exercise, external power, oxygen uptake, heart rate and blood lactate were significantly changed, while there were non-significant or only small changes to cycle rate, cycle length and ratings of perceived exertion. Incremental maximal tests showed that time to exhaustion was significantly changed and this occurred without a change in maximal power, maximal oxygen uptake, maximal heart rate and blood lactate, and that the influence on ratings of perceived exertion was non-significant or small.The study of classical style roller skis μS showed values that were five to eight times more than the values of μS reported from on-snow skiing with grip-waxed cross-country skis.The subsequent physiological and biomechanical experiments with different μS showed a significantly lower skiing economy (~14 % higher v̇O2), higher heart rate, lower propulsive forces coming from the legs and shorter time to exhaustion (~30 %) when using a different type of roller ski with a μS similar to on-snow skiing, while there was no difference between tests when using different pairs of roller skis with a (similar) higher μS.The part of the thesis which focused on skiing economy and efficiency as a function of skill, age and gender, showed that the elite cross-country skiers had better skiing economy and higher gross efficiency (5-18 %) compared with the recreational skiers, and the senior elite had better economy and higher efficiency (4-5 %) than their junior counterparts, while no differences could be found between the genders. / Syftet med denna avhandling var att undersöka fristils- och klassiska rullskidors rullmotståndskoefficienter (μR) och klassiska rullskidors statiska friktionskoefficienter (μS) samt effekter av olika μR och μS på längdskidåkares prestation vid rullskidåkning på rullande band. Syftet var även att undersöka s.k. åkekonomi och mekanisk verkningsgrad mellan motionärer och kvinnliga och manliga junior- och seniorlängdskidåkare på elitnivå.Experimenten visade att under en period av 30 minuters kontinuerligt rullande, på rullande band, så sjönk μR signifikant (p&lt;0.05) till 60-65 % och 70-75 % av initiala värden, för fristils- respektive klassiska rullskidor. Undersökandet av olika normalkrafter, hastigheter och lutningars påverkan på μR resulterade i en signifikant, negativ korrelation för μR som funktion av normalkraft, medan olika hastigheter och lutningar endast medförde små förändringar av μR.Studien som undersökte fysiologiska effekter av olika μR visade, vid submaximala konstanta arbetsbelastningar, att yttre effekt, syreupptagning, hjärtfrekvens och blodlaktat förändrades signifikant vid ~50 % förändring av μR. Försökspersonernas frekvens och sträcka per frekvens samt skattning av upplevd ansträngning resulterade dock i mestadels icke signifikanta eller små förändringar. Protokollen med successivt ökande arbetsbelastning (maxtest) resulterade i signifikant förändrad tid till utmattning, vid ~50 % förändring av μR. Detta inträffade utan signifikant skillnad i maximal syreupptagning, hjärtfrekvens och blodlaktat, vilket även mestadels gällde för skattning av upplevd ansträngning.Experimenten som undersökte klassiska rullskidors μS visade att dessa erhöll värden som är fem till åtta gånger högre än vad som rapporterats från studier av μS på snö med fästvallade skidor.Den efterföljande studien som undersökte fysiologiska och biomekaniska influenser av olika μS visade, vid submaximala konstanta arbetsbelastningar, att åkekonomin försämrades (~14 % högre syreförbrukning), hjärtfrekvensen ökade, den framåtdrivande kraften från benen på rullskidorna minskade samt att det blev kortare tid till utmattning (~30 %), vid maxtest, när skidåkarna använde rullskidor med en μS i likhet med vad som rapporterats för skidåkning på snö. För arbetsförsöken med olika rullskidor av olika fabrikat med en högre, och likartad, μS förelåg ingen skillnad i de undersökta variablerna.Studien som undersökte åkekonomi och mekanisk verkningsgrad som funktion av prestationsnivå, ålder och kön, visade att elitskidåkarna hade bättre åkekonomi och verkningsgrad (5-18 %) i jämförelse med motionärerna, att seniorerna hade bättre åkekonomi och verkningsgrad (4-5 %) än juniorerna och att ingen skillnad kunde konstateras mellan könen.

In this thesis we discuss different types of regularity for distributions which appear in the theory of pseudo-differential operators and partial differential equations. Partial differential equations often appear in science and technology. For example the Schrödinger equation can be used to describe the change in time of quantum states of physical systems. Pseudo-differential operators can be used to solve partial differential equations.  They are also appropriate to use when modeling different types of problems within physics and engineering. For example, there is a natural connection between pseudo-differential operators and stationary and non-stationary filters in signal processing. Furthermore, the correspondence between symbols and operators when passing from classical mechanics to quantum mechanics essentially agrees with symbols and operators in the Weyl calculus of pseudo-differential operators. In this thesis we concentrate on investigating how regularity properties for solutions of partial differential equations are affected under the mapping of pseudo-differential operators, and in particular of the free time-dependent Schrödinger operators. The solution of the free time-dependent Schrödinger equation can be expressed as a pseudo-differential operator, with non-smooth symbol, acting on the initial condition. We generalize a result about non-tangential convergence, which was obtained by Sjögren and Sjölin (1989) for the free time-dependent Schrödinger equation. Another way to describe regularity for a distribution is to use wave-front sets. They do not only describe where the singularities are, but also the directions in which these singularities appear. The first types of wave-front sets (analytical wave-front sets) were introduced by Sato (1969, 1970). Later on Hörmander introduced ``classical'' wave-front sets (with respect to smoothness) and showed results in the context of pseudo-differential operators with smooth symbols, cf. Hörmander (1985). In this thesis we consider wave-front sets with respect to Fourier Banach function spaces. Roughly speaking, we take B as a Banach space, which is invariant under translations and embedded between the space of Schwartz functions and the space of temperated distributions. Then we say that the wave-front set of a distribution contains all points (x0, ξ0) such that no localization of the distribution at x0, belongs to FB in the direction ξ0. We prove that pseudo-differential operators with smooth symbols shrink the wave-front set and we obtain opposite embeddings by using sets of characteristic points of the operator symbols. / I denna avhandling diskuterar vi olika typer av regularitet för distributioner som uppkommer i teorin för pseudodifferentialoperatorer och partiella differentialekvationer. Partiella differentialekvationer förekommer inom naturvetenskap och teknik. Exempelvis kan Schrödingerekvationen användas för att beskriva förändringen med tiden av kvanttillstånd i fysikaliska system. Pseudodifferentialoperatorer kan användas för att lösa partiella differential\-ekvationer. De användas också för att modellera olika typer av problem inom fysik och teknik. Det finns till exempel en naturlig koppling mellan pseudodifferentialoperatorer och stationära och icke-stationära filter i signalbehandling. Vidare gäller att relationen mellan symboler och operatorer vid övergången från klassisk mekanik till kvantmekanik i huvudsak överensstämmer med symboler och operatorer inom Weylkalkylen för pseudodifferentialoperatorer. I den här avhandlingen koncentrerar vi oss på att undersöka hur regularitetsegenskaper för lösningar till partiella differentialekvationer påverkas under verkan av pseudodifferentialoperatorer, och speciellt för de fria tidsberoende Schrödingeroperatorerna. Lösningen av den fria tidsberoende Schrödingerekvationen kan uttryckas som en pseudodifferentialoperator, med icke-slät symbol, verkande på begynnelsevillkoret. Vi generaliserar ett resultat om icke-tangentiell konvergens av Sjögren och Sjölin (1989) för den fria tidsberoende Schrödingerekvationen. Ett annat sätt att beskriva regularitet hos en distribution är med hjälp av vågfrontsmängder. De beskriver inte bara var singulariteterna finns, utan också i vilka riktningar dessa singulariteter förekommer. De första typerna av vågfrontsmängder (analytiska vågfrontsmängder) introducerades av Sato (1969, 1970). Senare introducerade Hörmander ''klassiska'' vågfrontsmängder (med avseende på släthet) och visade resultat för verkan av pseudodifferentialoperatorer med släta symboler, se  Hörmander (1985). I denna avhandling betraktar vi vågfrontsmängder med avseende på Fourier Banach funktionsrum. Detta kan ses som att vi låter B vara ett Banachrum, som är invariant under translationer och är inbäddat mellan rummet av Schwartzfunktioner och rummet av tempererade distributioner. Vågfrontsmängden av en distribution innehåller alla punkter (x0, ξ0) så att ingen lokalisering av distributionen kring x0, tillhör FB i riktningen ξ0. Vi visar att pseudodifferentialoperatorer med släta symboler krymper vågfrontsmängden och vi får motsatta inbäddningar med hjälp mängder av karakteristiska punkter till operatorernas symboler.

El objetivo fundamental de este trabajo ha sido el estudio del sistema fundamental de paralelos de un cuerpo convexo (conjunto compacto y convexo) en el espacio euclídeo n-dimensional. Se ha llevado a cabo siguiendo tres líneas diferentes: el estudio del polinomio de Steiner y el polinomio alternado Steiner desde el punto de vista algebraico de sus raíces y la conjetura de Matheron; el estudio de la diferenciabilidad de las quermassintegrales asociadas al cuerpo con respecto al parámetro de definición del sistema completo de paralelos y, por último, el estudio de las quermassintegrales del cuerpo desde el punto de vista analítico proporcionado por la identificación del cuerpo convexo con su función soporte, las propiedades de ésta cuando el cuerpo es suficientemente suave y la desigualdad de Brunn-Minkowski. / The aim of this work consists on studying the full system of parallel bodies of a convex body (compact and convex set) in the n-dimensional Euclidean space. It has been carried out following three different lines of work: the study of the Steiner polynomial and the alternating Steiner polynomial from the algebraic point of view of its roots; the study of the differentiability of the quermassintegrals associated to the convex body with respect to the parameter that defines the full system of parallel bodies and finally, the study of the quermassintegrals from the analytical point of view provided by the identification of a convex body with its support function, the properties of this function when the body is smooth enough and the Brunn-Minkowski inequality

La Tesis Doctoral está dedicada al estudio de ciertas propiedades de los radios sucesivos de los cuerpos convexos (funcionales definidos a partir de circunradios e inradios de proyecciones o secciones del cuerpo). Comenzamos estableciendo las nociones básicas necesarias para el desarrollo de los contenidos. A continuación calculamos los radios sucesivos de familias particulares de conjuntos (p-bolas, anchura constante, cuerpos tangenciales), y estudiamos la conexión existente entre estos funcionales y los números de Gelfand y Kolmogorov. En el tercer capítulo consideramos el problema de Pukhov-Perel'man sobre la mejor cota superior para un cierto cociente de radios, determinando desigualdades para problemas de este tipo que van a permitir mejorar los resultados existentes en ciertos casos. Finalmente, estudiamos cómo se relacionan los radios sucesivos de la suma de Minkowski (Firey) de dos cuerpos convexos con los correspondientes funcionales de los conjuntos, obteniendo los resultados óptimos en todos los casos. / The Doctoral Thesis is focused in the study of some properties of the successive radii of convex bodies (functionals defined by means of circumradii and inradii of projections or sections of the set). We start establishing the basic notions that will be needed further on. Next, we compute the successive radii of particular families of sets (p-balls, constant width sets and tangential bodies), and study the connection between these functionals and the Gelfand and Kolmogorov numbers. In the third chapter we consider the Pukhov-Perel'man problem on the best upper bound for a particular ratio of radii, determining inequalities for some problems of this type which will allow to improve the known results in particular cases. Finally we study how the successive radii of the (Firey)-Minkowski addition of two convex bodies are related with the corresponding functionals of the sets, obtaining the optimal results in all cases.

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This diploma thesis deals with the comparative analysis of the physiological, degenerative and postoperative state of the lumbar spine. The problem was solved by computational modeling using the finite element method. For this solution, it was necessary to create appropriate computational models. The spine physiological state was compared with cases of the lumbar spine with different levels of spondylolisthesis, cases of the lumbar spine with different sacral angles, and cases of lumbar spine with applied fixators. Based on the performed analyses, it was found that spine degenerative state has a great influence on the distribution of stress in the vertebral discs and the vertebra itself. Compared to the physiological state, with increasing level of the spondylolisthesis the stress in the vertebral discs increases, while the stress in the vertebral section decreases. Furthermore, the spondylolisthesis affects the force flow. The higher the level of the spondylolisthesis, the more the force flow is shifted onto the posterior articular ligaments. The best results in terms of the spine physiological state were achieved with the applied fixator model.

Background: The focus of this study was to investigate how producing human bone marrow (hBM) derived mesenchymal stromal cell (MSC) extracellular vehicles (EVs) in a high purity isolation system would affect their established characterization criteria and address the validity of these methods of EV production. Additionally, we set out to functionally characterize the hBM-MSC-EVs for their identified immunomodulatory ability while also assessing the presence of novel MSC-EV marker NRP1 identified by our group to further affirm its validity as a functional MSC-EV identity marker. Methods: Each hBM-MSC-EV donor was cultured in a hollow-fiber bioreactor system in non-stimulating serum/xeno-free conditions for 25 days to produce EVs persistently under quiescent conditions to characterize the hBM-MSC-EVs in their native form. EVs were isolated by traditional PEG-based precipitation for preliminary characterization to monitor bioreactor production wherein they were characterized using multimodal tangential flow filtration coupled with fast protein liquid chromatograph (FPLC) size exclusion/high-affinity purifications to obtain the final highly purified EV sample. Additionally, functional analysis of their immunomodulatory ability, EVs and MSCs were incubated with activated peripheral blood mononuclear cells (PBMCs) as an in-vitro model to evaluate their potency. Results: The hBM-MSC-EVs produced from the bioreactor system showed consistent characterization in accordance with the MISEV2018 establish criteria. We were also able to demonstrate their functional ability by observing statistically significantly immunomodulatory ability of activated PBMCs equivalent to native MSC ability. We were also able to validate the present of NRP1 on all hBM-MSC-EV samples produced confirming its validity as a MSC-EV marker. Conclusion: The significance of the results obtained from this study confirms the production of MSC-EV using a bioreactor and high purity isolation for obtaining consistent MSC-EVs for downstream investigation. Additionally, we were able to demonstrate the significance of MSC-EVs on MSC signaling for immunomodulation by showing equivalent functional potency when tested in-vitro. These results contribute to further understanding the biological attributes of MSC-EVs and contribute to the validation of currently established characterization guidelines.