Microencapsulation and transplantation of genetically engineered cells: a new approach to somatic gene therapy

In order to develop a model for gene therapy which avoids dependence on an autologous source of target cells and immunosuppressive therapy, mouse Ltk fibroblasts transfected with a human growth hormone (hGH) fusion gene were encapsulated in a semipermeable alginate-poly-L-lysine-alginate (APA) membrane. The encapsulated cells were cultured in vitro or transplanted intraperitoneally into mice to monitor cell viability, cell growth, and hGH secretion. The effect of Zn2+ ions on vector expression was also monitored in vitro and in vivo. Results indicate that: (1) the capsule environment is compatible with cell viability and cell growth; (2) the capsule limits cell growth; (3) the capsule membrane is permeable to the exit of hGH; (4) gene product expression may be stimulated by external means; (5) the novel gene product is delivered in vivo; and (6) encapsulated cells recovered from transplant recipients continue to secrete hGH in vitro. The results suggest therapeutic potential of this approach to somatic gene therapy.