Delivery of Recombinant Gene Products to the Central Nervous System with Nonautologous Cells in Alginate Microcapsules

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Abstract
Somatic gene therapy using nonautologous recombinant cells immunologically protected with alginate migenetic crocapsules has been successfully used to treat rodent diseases. We now report the delivery of re- combinant gene products to the brain in rodents by implanting microencapsulated cells for the purpose of eventually treating neurodegenerative diseases with this technology. Alginate-poly-L-lysine-alginate micro- capsules enclosing mouse C2C12 myoblasts expressing the marker gene human growth hormone (hGH) at 95 +/- 20 ng/million cells/hr were implanted into the right lateral ventricles of mice under stereotaxic guidance. Control mice were implanted similarly with nontransfected but encapsulated cells. Delivery of hGH to the different regions of the brain at various times postimplantation was examined. At 7, 28, 56, and 112 days postimplantation, hGH was detected at high levels around the implantation site and also at lower levels in the surrounding regions, while control mice showed no signal. Immunohistochemical staining of the implanted brains showed that on days 7, 56, and 112 postimplantation, hGH was localized in the tissues around the imc- plantation site. Mice implanted with encapsulated but nontransfected cells showed no signal. Hence, the fea- sibility of using encapsulated nonautologous cells to deliver recombinant gene products to the brain for ex- tended periods may allow the application of this technology to the treatment of neurodegenerative genetic disorders.

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