Delivery of recombinant gene products with microencapsulated cells in vivo.
If established cultured cell lines genetically modified to secrete desired gene products could be implanted in different allogeneic recipients without immune rejection, novel gene products would be delivered more cost effectively. We tested this strategy by encapsulating mouse Ltk- cells transfected with the human growth hormone (hGH) gene in immunoprotective perm-selective alginate microcapsules. Allogeneic mice implanted with these microcapsules demonstrated hGH in their circulation (0.1-1.5 ng/ml serum) within the first 2 weeks. Control mice implanted with only the transfected cells without microcapsules did not demonstrate significant levels of circulating hGH. By about 3 weeks, antibodies against hGH developed in the microcapsule-implanted mice. The immune response was detected only against the hGH and no other secretory products from the transfected cells. The antibody titer continued to escalate for more than three months, thus demonstrating indirectly the continued delivery of the growth hormone. The persistent expression of the transgene and survival of the transfected cells were verified when the microcapsules were retrieved periodically to demonstrate that the encapsulated cells remained viable, proliferative, and productive of hGH even by 78-111 days. In conclusion, delivering gene products with genetically modified allogeneic cells in vivo has been shown feasible for prolonged periods. This technology should have potential applications in somatic gene therapy and in treatment of other somatic diseases.
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
P L
PL
Chang
N
N
Shen
A J
AJ
Westcott
D000818:Animals; D001483:Base Sequence; D002214:Capsules; D002460:Cell Line; D017931:DNA Primers; D004343:Drug Implants; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation; D015316:Genetic Therapy / Q000379:methods*; D013006:Growth Hormone / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D014162:Transfection
D002214:Capsules; D017931:DNA Primers; D004343:Drug Implants; D011994:Recombinant Proteins; D013006:Growth Hormone