Tesiak

Multifunctional systems based on microencapsulated cells: advances in biosafety and biocompatibility

Doktoregaia:
Argia Acarregui Garalde
Urtea:
2014
Unibertsitatea:
Faculty of Pharmacy. University of the Basque Country
Zuzendaria(k):
Rosa Mª Hernández, Gorka Orive
Deskribapena:

Microencapsulation of cells represents a pharmaceutical strategy for the controlled release of therapeutic products over long periods of time. The correct selection of cell lines as well as an optimal technological development of immobilization systems allows this technology to be applied to the treatment of multiple pathologies. In this doctoral thesis, several milestones in this technology related to biosafety and the improvement of biocompatibility have been addressed. These include improving the localization and monitoring of microencapsulated cells in real time, optimizing administration and retention protocols for these microcapsules, and designing combined systems to prevent host immune rejection, thus developing a cell encapsulation system marked with Endorem® contrast agent (magnetocapsules) to increase cell retention and survival and improve cell tracking in an animal model. The results obtained showed that the immobilized cells in the magnetocapsules probably act as a continuous and localized release system of growth factors and cytokines allowing the damaged myocardial tissue to regenerate. The results showed that these biosystems prevent dissemination, ensure localization and facilitate the extraction of microcapsules. Finally, a combined system was developed based on the administration of encapsulated cells and biodegradable PLGA microspheres loaded with dexamethasone in an alginate hydrogel. The system developed increased the viability and functionality of the implanted cells. The administration of the formulation with a single injection could be the most suitable guideline to improve patient compliance and comfort, and the results derived from this doctoral thesis open up new possibilities in the field of cell therapy, turning microencapsulation of cells into a promising therapeutic alternative for chronic diseases that currently lack effective treatment.

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