Immunoprotective Encapsulation of Micro-Organs

Background: Cell encapsulation technology is most likely the ultimate solution for cell therapy based clinical approaches. A key issue when developing a functional encapsulated construct is to consider not only the nature of the capsule but also how the cells should be incorporated into the capsule in order to minimally compromise their function. Methods: We have developed a tissue engineering approach, composed of decellularized micro scaffolds and various types of cells in which fully functional “Engineered Micro-Organs” (EMOs) are formed. Based on this technology, Engineered Micro-Pancreata (EMPs), made by seeding human islets into acellular micro-scaffolds, have been shown to remain viable, and to secrete high levels of insulin in a regulated manner as a function of glucose comparable to those secreted by fresh human islets in culture for long periods. We now report the development of a novel encapsulation approach that takes into account the structure and diffusion requirements of the encapsulated construct. Results: We here report the development of a capsule in which encapsulated EMPs, when implanted into xenogeneic mice, induced the formation of a fine vascular network and continued to secrete human insulin in a glucose regulated manner for several weeks. Furthermore, encapsulated EMOs remained viable for at least three months in vivo with no penetration of xenogeneic host cells into the capsule chamber. Conclusions: The results show that the capsule presented is sturdy and resilient to biodegradation. Moreover, it not only protects the functional cells from rejection but also ensures that cells would remain secluded in the chamber, thus avoiding, in the case of stem cells or others, the chances of tumor formation. These results are also important in future approaches to create micro-organ types of structures based on embryonic stem cells.