Continuous and high-level in vivo delivery of endostatin from recombinant cells encapsulated in TheraCyte immunoisolation devices.

Abstract:

:Endostatin (ES) is a potent inhibitor of angiogenesis and tumor growth. Continuous ES delivery of ES improves the efficacy and potency of the antitumoral therapy. The TheraCyte system is a polytetrafluoroethylene (PTFE) semipermeable membrane macroencapsulation system for implantation of genetically engineered cells specially designed for the in vivo delivery of therapeutic proteins, such as ES, which circumvents the problem of limited half-life and variation in circulating levels. In order to enable neovascularization at the tissues adjacent to the devices prior to ES secretion by the cells inside them, we designed a scheme in which empty TheraCyte devices were preimplanted SC into immunodeficient mice. Only after healing (17 days later) were Chinese hamster ovary cells expressing ES injected into the preimplanted devices. In another model for device implantation, the cells expressing ES where loaded into the immunoisolation devices prior to implantation into the animals, and the TheraCyte were then immediately implanted SC into the mice. Throughout the 2-month study, constant high ES levels of up to 3.7 microg/ml were detected in the plasma of the mice preimplanted with the devices, while lower but also constant levels of ES (up to 2.1 microg/ml plasma) were detected in the mice that had received devices preloaded with the ES-expressing cells. Immunohistochemistry using anti-ES antibody showed reaction within the device and outside it, demonstrating that ES, secreted by the confined recombinant cells, permeated through the membrane and reached the surrounding tissues.

journal_name

Cell Transplant

journal_title

Cell transplantation

authors

Malavasi NV,Rodrigues DB,Chammas R,Chura-Chambi RM,Barbuto JA,Balduino K,Nonogaki S,Morganti L

doi

10.3727/096368909X480927

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

269-77

issue

3

eissn

0963-6897

issn

1555-3892

pii

ct2079malavasi

journal_volume

19

pub_type

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