Myriam Cilla

Epicardial delivery of collagen patches with adipose-derived stem cells in rat and minipig models of chronic myocardial infarction.

Although transplantation of adipose-derived stem cells (ADSC) in chronic myocardial infarction (MI) models is associated with functional improvement, its therapeutic value is limited due to poor long-term cell engraftment and survival. Thus, the objective of this study was to examine whether transplantation of collagen patches seeded with ADSC could enhance cell engraftment and improve cardiac function in models of chronic MI. With that purpose, chronically infarcted Sprague-Dawley rats (n = 58) were divided into four groups and transplanted with media, collagen scaffold (CS), rat ADSC, or CS seeded with rat ADSC (CS-rADSC). Cell engraftment, histological changes, and cardiac function were assessed 4 months after transplantation. In addition, Göttingen minipigs (n = 18) were subjected to MI and then transplanted 2 months later with CS or CS seeded with autologous minipig ADSC (CS-pADSC). Functional and histological assessments were performed 3 months post-transplantation. Transplantation of CS-rADSC was associated with increased cell engraftment, significant improvement in cardiac function, myocardial remodeling, and revascularization. Moreover, transplantation of CS-pADSC in the pre-clinical swine model improved cardiac function and was associated with decreased fibrosis and increased vasculogenesis. In summary, transplantation of CS-ADSC resulted in enhanced cell engraftment and was associated with a significant improvement in cardiac function and myocardial remodeling.

Machine Learning Techniques as a Helpful Tool Toward Determination of Plaque Vulnerability

Atherosclerotic cardiovascular disease results in millions of sudden deaths annually, and coronary artery disease accounts for the majority of this toll. Plaque rupture plays main role in the majority of acute coronary syndromes. Rupture has been usually associated with stress concentrations, which are determined mainly by tissue properties and plaque geometry. The aim of this study is develop a tool, using machine learning techniques to assist the clinical professionals on decisions of the vulnerability of the atheroma plaque. In practice, the main drawbacks of 3-D finite element analysis to predict the vulnerability risk are the huge main memories required and the long computation times. Therefore, it is essential to use these methods which are faster and more efficient. This paper discusses two potential applications of computational technologies, artificial neural networks and support vector machines, used to assess the role of maximum principal stress in a coronary vessel with atheroma plaque as a function of the main geometrical features in order to quantify the vulnerability risk.

Towards the modelling of ageing and atherosclerosis effects in ApoE-/- mice aortic tissue

The goal of this work consists in a quantitative analysis and constitutive modelling of ageing processes associated to plaque formation in mice arteries. Reliable information on the characteristic evolution of pressure-stretch curves due to the ageing effects is extracted from previous inflation test experiments. Furthermore, characteristic age-dependent material parameters are identified on the basis of a continuum-mechanics-based parameter optimisation technique. The results indicate that the aorta-stiffness of the healthy control mice remains basically constant irrespective of the diet-time and age. In contrast, significant differences exist within the material response and in consequence within the material parameters between the ApoE(-/-) and the control mice as well as for the different locations over the aorta which is underlined by our experimental observations. With regard to the temporal evolution of the material parameters, we observe that the material parameters for the ApoE(-/-) mice aortas exhibit a saturation-type increase with respect to age.

Sost deficiency leads to reduced mechanical strains at the tibia midshaft in strain-matched in vivo loading experiments in mice

Sclerostin, a product of the Sost gene, is a Wnt-inhibitor and thus negatively regulates bone accrual. Canonical Wnt/β-catenin signalling is also known to be activated in mechanotransduction. Sclerostin neutralizing antibodies are being tested in ongoing clinical trials to target osteoporosis and osteogenesis imperfecta but their interaction with mechanical stimuli on bone formation remains unclear. Sost knockout (KO) mice were examined to gain insight into how long-term Sost deficiency alters the local mechanical environment within the bone. This knowledge is crucial as the strain environment regulates bone adaptation. We characterized the bone geometry at the tibial midshaft of young and adult Sost KO and age-matched littermate control (LC) mice using microcomputed tomography imaging. The cortical area and the minimal and maximal moment of inertia were higher in Sost KO than in LC mice, whereas no difference was detected in either the anterior–posterior or medio-lateral bone curvature. Differences observed between age-matched genotypes were greater in adult mice. We analysed the local mechanical environment in the bone using finite-element models (FEMs), which showed that strains in the tibiae of Sost KO mice are lower than in age-matched LC mice at the diaphyseal midshaft, a region commonly used to assess cortical bone formation and resorption. Our FEMs also suggested that tissue mineral density is only a minor contributor to the strain distribution in tibial cortical bone from Sost KO mice compared to bone geometry. Furthermore, they indicated that although strain gauging experiments matched strains at the gauge site, strains along the tibial length were not comparable between age-matched Sost KO and LC mice or between young and adult animals within the same genotype.

Machine learning techniques for the optimization of joint replacements: Application to a short-stem hip implant

Today, different implant designs exist in the market; however, there is not a clear understanding of which are the best implant design parameters to achieve mechanical optimal conditions. Therefore, the aim of this project was to investigate if the geometry of a commercial short stem hip prosthesis can be further optimized to reduce stress shielding effects and achieve better short-stemmed implant performance. To reach this aim, the potential of machine learning techniques combined with parametric Finite Element analysis was used. The selected implant geometrical parameters were: total stem length (L), thickness in the lateral (R1) and medial (R2) and the distance between the implant neck and the central stem surface (D). The results show that the total stem length was not the only parameter playing a role in stress shielding. An optimized implant should aim for a decreased stem length and a reduced length of the surface in contact with the bone. The two radiuses that characterize the stem width at the distal cross-section in contact with the bone were less influential in the reduction of stress shielding compared with the other two parameters; but they also play a role where thinner stems present better results.

A 3D PARAMETRIC STUDY OF ECCENTRIC ATHEROMA PLAQUE: INFLUENCE OF GEOMETRICAL FACTORS AND RESIDUAL STRESSES

The aim of this study is to evaluate the influence of morphology on the risk of plaque rupture, including main geometrical factors, and to assess the role of circumferential and axial residual stresses by means of a parametric 3D finite element model. For this purpose, a 3D parametric finite element model of the coronary artery with eccentric atheroma plaque was developed. Healthy (adventitia and media in areas without atheroma plaque) and diseased (fibrotic and lipidic) tissues were considered in the model.

MECHANICAL PROPERTIES OF ATHEROMA PLAQUE ALONG THE LENGTH OF THE AORTA IN APOE−/− MICE MODEL

Numerous animal species have been used to study the pathogenesis and potential treatment of the lesions of atherosclerosis. The apolipoprotein Edeficient transgenic mice (ApoE-/-) created by homologous recombination in embryonic stem cells, have been shown to develop severe hypercholesterolemia and lesions of atherosclerosis more characteristic in appearance and distribution to those observed in humans [Plump A. et al,1992]. The main goal of the present work was to study the progressive stiffening of the aorta in Apo-E and healthy mice for different ages.