Encapsulation of Transgenic Cells for Gene Therapy

Abstract

A major challenge to emerging cell-based medicine including gene therapy is the host immune rejection of transplanted donor cells or engineered tissue. One way to address this problem is to use drugs to achieve immunosuppression. However, suppressing the patient's immune system may put the patient at risk for many other diseases. An alternative is to encapsulate living cells in macro/microcapsules to achieve immunoisolation of the cells, thereby increasing cell viability in the patient's body following transplantation. The capsule's membrane protects the encapsulated cells from being damaged by both the host's immune system and mechanical stress while allowing free diffusion of nutrients and metabolic waste for the cells to survive. Moreover, the membrane could be designed to achieve controlled and/or sustained release of therapeutic products produced by the encapsulated transgenic cells to treat a variety of diseases such as cardiovascular disorders, anemia, wounds, bone fractures, and cancer.

Design of Artificial Red Blood Cells using Polymeric Hydrogel Microcapsules: Hydrogel Stability Improvement and Polymer Selection

“…5). Alginates, being polysaccharides, are linear block polymers, consisting of α-L-guluronic acid (G) and β-D-manuronic acid (M) blocks (23). Pectin is a naturally occurring polysaccharide composed of galacturonic acid with carboxyl groups.…”

“…It is also of great interest and importance to explore the possibilities of using other biopolymers for creating redblood-cell-shaped hydrogel microcapsules. Alginate was chosen during this study, since it can form hydrogels through divalent cation cross-linking or polyelectrolyte formation like pectin does (23). Alginate has been one of the most commonly used biomaterials for tissue engineering and regenerative medicine, due to its natural origin (mainly from seaweeds) and excellent biocompatibility (24)(25)(26)(27).…”

Bioencapsulation Technologies in Tissue Engineering

“…However, their product quality and characteristics can vary broadly among resources and batches. It is well known that a natural polymer’s purity and composition, such as the guluronic and mannuronic acid ratio of alginate, highly influence the capsule’s performance (21–23). Synthetic polymers such as poly(ethylene glycol) (PEG), 2-hydroxyethyl methacrylate (HEMA) and poly(lactic- co -glycolic acid) (PLGA) exhibit more consistent chemical compositions and molecular weights due to the minimized batch-to-batch variations (4, 23–25).…”

“…It is well known that a natural polymer’s purity and composition, such as the guluronic and mannuronic acid ratio of alginate, highly influence the capsule’s performance (21–23). Synthetic polymers such as poly(ethylene glycol) (PEG), 2-hydroxyethyl methacrylate (HEMA) and poly(lactic- co -glycolic acid) (PLGA) exhibit more consistent chemical compositions and molecular weights due to the minimized batch-to-batch variations (4, 23–25). Unfortunately, when using synthetic polymers for bioencapsulation, unfavorable conditions are often inevitable, such as exposure to UV light and nonphysiological pH and/or temperature conditions (25).…”

“…Although bioencapsulation technologies show great promise for tissue engineering, there are still several issues that need to be addressed for eventual clinical applications, including limited cell resources, protrusion of encapsulated cells and scaling-up (especially following Good Manufacturing Practice (GMP) guidelines) (2,23,(74)(75)(76). The recent progress of stem cell research prominently expands cell resources for bioencapsulation, addressing the first limitation (77).…”