In vivo delivery of recombinant human growth hormone from genetically engineered human fibroblasts implanted within Baxter immunoisolation devices

Continuous delivery of therapeutic peptide to the systemic circulation would be the optimal treatment for a variety of diseases. The Baxter TheraCyte system is a membrane encapsulation system developed for implantation of tissues, cells such as endocrine cells or cell lines genetically engineered fo...

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Bibliographic Details
Published in:Journal of molecular medicine (Berlin, Germany) Germany), 1999, Vol.77 (1), p.211-214
Main Authors: JOSEPHS, S. F, LOUDOVARIS, T, DIXIT, A, YOUNG, S. K, JOHNSON, R. C
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Line
Cell Transplantation
Encapsulation
Fibroblasts - metabolism
Fibroblasts - transplantation
Genetic Engineering
Genetic Therapy - methods
Human Growth Hormone - biosynthesis
Human Growth Hormone - blood
Human Growth Hormone - genetics
Humans
Medical sciences
Membranes, Artificial
Miscellaneous
Rats
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
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Summary:Continuous delivery of therapeutic peptide to the systemic circulation would be the optimal treatment for a variety of diseases. The Baxter TheraCyte system is a membrane encapsulation system developed for implantation of tissues, cells such as endocrine cells or cell lines genetically engineered for therapeutic peptide delivery in vivo. To demonstrate the utility of this system, cell lines were developed which expressed human growth hormone (hGH) at levels exceeding 1 microgram per million cells per day. These were loaded into devices which were then implanted into juvenile nude rats. Significant levels of hGH of up to 2.5 ng/ml were detected in plasma throughout the six month duration of the study. In contrast, animals implanted with free cells showed peak plasma levels of 0.5 to 1.2 ng four days after implantation with no detectable hGH beyond 10 days. Histological examination of explanted devices showed they were vascularized and contained cells that were viable and morphologically healthy. After removal of the implants, no hGH could be detected which confirmed that the source of hGH was from cells contained within the device. The long term expression of human growth hormone as a model peptide has implications for the peptide therapies for a variety of human diseases using membrane encapsulated cells.
ISSN:0946-2716
1432-1440
DOI:10.1007/s001090050338