A novel approach that preserved most mesenchymal stem cell (MSC) characteristics was developed using MSC encapsulation in a hydrogel based on hyaluronic acid (HA). An optimized HA-hydrogel composition, whose characteristics were assessed by scanning electron microscopy and viscoelastic property analyses, as well as the more favorable MSC seeding density, was established. These optimal three-dimensional MSC culture conditions allowed morphological cell remodeling, maintained the expression of stem cell markers over 28 days of culture, and preserved MSC differentiation plasticity. In addition, MSCs in HA-hydrogel submitted for 7 days to mechanical constraint that aimed at mimicking in vivo cardiac beat displayed enhanced cell survival by more than 40% compared to static culture conditions. Thus, the optimized HA-based hydrogel provides a niche for MSCs, which preserves their properties and opens ways for cell therapy, in particular in aortic repair medicine.
A stochastic mechanical model using the membrane theory was used to simulate the in vivo mechanical behaviour of abdominal aortic aneurysms (AAAs) in order to compute the wall stresses after stabilisation by gene therapy. For that, both length and diameter of AAAs rats were measured during their expansion. Four groups of animals, control and treated by an endovascular gene therapy during 3 or 28 days were included. The mechanical problem was solved analytically using the geometric parameters and assuming the shape of aneurysms by a 'parabolic-exponential curve'. When compared to controls, stress variations in the wall of AAAs for treated arteries during 28 days decreased, while they were nearly constant at day 3. The measured geometric parameters of AAAs were then investigated using probability density functions (pdf) attributed to every random variable. Different trials were useful to define a reliable confidence region in which the probability to have a realisation is equal to 99%. The results demonstrated that the error in the estimation of the stresses can be greater than 28% when parameters uncertainties are not considered in the modelling. The relevance of the proposed approach for the study of AAA growth may be studied further and extended to other treatments aimed at stabilisation AAAs, using biotherapies and pharmacological approaches.
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