Optimization of cell microencapsulation in terms of biosafety, biomimesis and applicability in therapeutic targets of central nervous system

Edorta Santos Vizcaino
Faculty of Pharmacy. University of the Basque Country
Personas encargadas de la dirección:
Jose Luis Pedraz, Gorka Orive.

On the basis of the results obtained in the experimental studies of thisdissertation, the following conclusions were derived:1. The incorporation of the pSFGNESTGL into cells resulted in an accurate toolfor holding a tight control over microencapsulated cells. More importantly,this method provided meaningful information about the functionality ofthe enclosed cells at desired time points and in a non-invasive way,avoiding the necessity to retrieve the implant. This would help todetermine the precise location of the therapeutic biosystems in vivo and tomonitor encapsulated cells in real-time.2. Encapsulated cells transduced with the TGL triple-fusion reporter genesuccessfully responded to GCV administration suffering apoptosis andleading to implant inactivation in vivo.3. The present work provided meaningful insight regarding GCV-mediatedinactivation process in encapsulated cells bearing TGL triple-fusionreporter gene through its fused HSV-TK suicide gene.4. The inclusion of inactivation gene vectors in the genome of encapsulatedcells may represent a valuable strategy to overcome some of the biosafetyconcerns in the field of cell microencapsulation. In this work, TGL triplefusionreporter gene demonstrated satisfactory results in regulating therelease of therapeutic factors, and it is proposed as a starting point towork in this direction.5. The present study covered a comprehensive technological development toachieve an 80% size reduction of classic APA microcapsules and obtainhighly monodisperse 100 ¿m particles while preserving cell viability andfunction. In addition, this work reinforced the suitableness of APA capsuleseven at this particular size.6. The final stage of this thesis entailed the optimization of intraocularadministration of 100 ¿m APAs and proved the correct adaptation of theimplant to the vitreous humor environment. This opens the doors tofurther investigations, where the effectiveness of this technology might betested in a retinopathy model.

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