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The FASEB Journal, Vol 7, 1061-1069, Copyright © 1993 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Microencapsulation of recombinant cells: a new delivery system for gene therapy

IT Tai and AM Sun
Department of Physiology, University of Toronto, Ontario, Canada.

The therapeutic potential of somatic gene therapy has been extensively investigated in recent years, yet its slow progression into the clinical setting can be attributed to problems associated with the inability to achieve efficient gene transfers, to obtain sustained level of expression of the transfected gene, and the necessity to avoid immunorejection after transplantation. Here we report on an alternate strategy in gene therapy that overcomes all three problems by immunoisolating genetically modified cells in a biocompatible membrane, thereby introducing a system that can provide sustained delivery of the desired gene product. As a model, mouse fibroblasts transformed with the human growth hormone gene (Ltk-GH) were encapsulated with an alginate-poly-L-lysine-alginate membrane. Long-term in vitro studies showed that the encapsulation of the cells was physiologically compatible with growth and survival of the cells. Furthermore, there was a unique pattern of secretion of the human protein by the encapsulated cells: there was a phase of steady increase in the secretion of the human growth hormone by each cell, followed by a plateau phase. The most convincing evidence of the feasibility of this strategy was provided by the in vivo study: Balb-c mice transplanted with encapsulated Ltk-GH cells had detectable serum levels of human growth hormone (hGH) for the duration of the study (115 days). Moreover, encapsulated cells recovered from a recipient 1 year after the transplantation continued to secrete high levels of hGH in culture.


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Copyright © 1993 by The Federation of American Societies for Experimental Biology.