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Nouvelles microcapsules fonctionnalisées et standardisées : Application à la thérapie cellulaire du diabète de type 1

Abstract : Cell therapy with allogenic pancreatic islets is a treatment used for type 1 diabetic patients for whom the usual insulin treatments does not work anymore. However, this therapy requires administration of an immunosuppressive treatment, that leads to many side effects and complications. The implantation of microencapsulated islets that become stealth to the host’s immune system consists in an alternative to immunosuppressive treatments. This technique presents very promising results in several clinical trials, but there are still many challenges that need to be tackled, to increase the durability of a functional graft. The FUTURCAPS project, in which this PhD is integrated, focused on improving two currently limiting points : the properties of the polymers used for the encapsulation, by using chemically modified alginates, that increase the mechanical stability of the capsules ; and the control in size and shape of the capsules, that enables to have an optimal diffusion barrier, by using a microfluidics flow focusing (MFFD) droplet generation system, developed at the CEA (Grenoble). To do this, the physicochemical properties of the different alginates were first characterized, and theoretical rheological models that define their behaviour were determined. Then, the parameters involved in the formation and gelation of the droplets were studied (viscosity, surface tension, contact angle, shear rate while forming the droplets, and gelation rate). Following these studies, monodisperse capsules (variation coefficients under 5 %) were obtained in microfluidics with the different alginates (that have very diverse properties), and these latter were characterized in terms of size, shape and permeability. Eventually, neo-natal pig, and human pancreatic islets were encapsulated in the alginates studied. The encapsulated islets viability was measured in vitro, and they have also been implanted in mice, in order to check for biotolerability and viability in vivo after 15 days.
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Submitted on : Friday, September 11, 2020 - 12:22:11 PM
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  • HAL Id : tel-02935632, version 2

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Roxane Crouigneau. Nouvelles microcapsules fonctionnalisées et standardisées : Application à la thérapie cellulaire du diabète de type 1. Médecine humaine et pathologie. Université Grenoble Alpes, 2019. Français. ⟨NNT : 2019GREAS033⟩. ⟨tel-02935632v2⟩

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