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.
Basic
D
D
Department of Physiology, Faculty of Medicine, University of Toronto, Ontario, Canada.
Vacek
I
I
Sun
A M
AM
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D017690:Cell Transplantation; D004339:Drug Compounding; D005347:Fibroblasts / Q000378:metabolism; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D051379:Mice; D015032:Zinc / Q000494:pharmacology
D019382:Human Growth Hormone; D015032:Zinc