Cell microencapsulation is a pharmaceutical strategy for the controlled release of therapeutic products over long periods of time. “The great versatility of this strategy allows microcapsules of varying sizes and cell composition to be manufactured so that the encapsulated cells can be used in the treatment of various diseases like neurodegenerative, hepatic, cardiovascular and endocrine disorders, among others,” said Argia Acarregui, researcher attached to the NanoBioCel research group of the UPV/EHU’s Faculty of Pharmacy.
Despite being an emerging field that is rapidly developing, “it is still at the lab stage. There are some clinical trials and where the most progress has been made is in the treatment of diabetes,” she added. In this case, groups of pancreatic cells are encapsulated and implanted in diabetic animals or people, so that the cells will produce insulin and regulate sugar levels. Acarregui points out that these systems for releasing drugs have the advantage of being “systems that continuously secrete the relevant drug in each case”.
Some of the challenges to be resolved before this technology can become a real proposal for clinical application have to do with biosafety, in other words, the possibility of monitoring the implanted microcapsules and monitoring them in real time. At the same time, even though the implanted cells are coated in a biocompatible membrane, immunological response against them is very frequent so it is “important to reduce immunological rejection and come up with systems that are totally biocompatible,” said Acarregui.
Marked capsules, hidrogel and immunomodulators
Acarregi tackled these challenges in three separate pieces of work. In the first, she developed and evaluated a system of encapsulation of cells marked with a contrast agent. As a result, the contrast agent enabled them to improve the monitoring of the microcapsules and, what is more, the encapsulation system increased cell retention and survival. In cell therapies for the heart, the problem of cell retention is a major one because the continual heartbeats reduce their permanence in the place where they are administered. “Thanks to these microcapsules, retention was greater and we were able to see that the encapsulated cells probably released growth factors and cytokines which allowed the damaged myocardial tissue to be regenerated in the animal model of infarction used,” said the researcher.
In a second piece of work, they managed to prevent dissemination, ensure the location and facilitate the extraction of the microcapsules by means of the design of a hydrogel into which they inserted the encapsulated cells because it kept them all together. “Besides,” said Acarregui, “there was found to be a reduction in the fibrotic layer which the immune response forms around these microcapsules.”
Finally, in a third piece of work they managed to prevent the immune response of the host to a greater extent. For the experiment they took encapsulated mouse cells and inserted them into rats, in other words, they did a xenotransplant, because in this type of transplant “immunological rejection tends to be even greater,” she explained. By using the same hydrogel as in the previous piece of work they combined the encapsulated cells with nanoparticles that were releasing dexamethasone, an immunomodulating agent, in a sustained way. “The system developed enabled the viability and functionality of the implanted cells to be increased,” she concluded, “since the immunomodulating agent added to the hydrogel managed to slow down the immunological response, thus increasing the time in which the implant remained functional.”
Argia Acarregui-Garalde (Ondarroa, Basque Country, 1985) conducted this study as part of her PhD thesis entitled Sistemas multifuncionales basados en células microencapsuladas: avances en bioseguridad y biocompatibilidad (Multifunctional systems based on microencapsulated cells: advances in biosafety and biocompatibility). The work was carried out in the Pharmacy and Pharmaceutical Technology Laboratory in the UPV/EHU’s department of Pharmacy and Food Sciences, where she currently works. For the first piece of work conducted, they had the collaboration of the Centro de Cirugía de Mínima Invasión Jesús Usón (Jesús Usón Centre for Minimum Invasion Surgery-CCMIJU) in Cáceres (Spain).
Acarregui A, Herrán E, Igartua M, Blanco FJ, Pedraz JL, Orive G, Hernández RM. 2014. “Multifunctional Hydrogel-Based Scaffold for Improving the Functionality of Encapsulated Therapeutic Cells and Reducing Inflammatory Response”. Acta Biomater. pii: S1742-7061(14)00294-3. doi: 10.1016/j.actbio.2014.06.038.