Construction of glomerular epithelial cells expressing both immune tolerance and GFP genes and application to cell therapy by cell transplantation |
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Authors: | Masahiro Ohga Mariko Ogura Mastoshi Matsumura Pi-Chao Wang |
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Institution: | (1) Institute of Applied Biochemistry, University of Tsukuba, 1-1-1 Tennodai, 305-8572 Tsukuba City, Japan |
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Abstract: | Cell therapy applied to wound healing or tissue regeneration presents a revolutionary realm to which principles of gene engineering
and delivery may be applied. One promising application is the transplantation of cells into the wounded tissue to help the
tissue repair. However, when cells are transplanted fromin vitro toin vivo, immune rejection occurs due to the immune response triggered by the activation of T-cell, and the transplanted cells are
destroyed by the attack of activated T-cell and lose their function. Immune suppressant such as FK506 is commonly used to
suppress immune rejection during transplantation. However, such kind of immune suppressants not only suppresses immune rejection
in the periphery of transplanted cells but also suppresses whole immune response system against pathogenic infection. In order
to solve this problem, we developed a method to protect the desired cells from immune rejection without impairing whole immune
system during cell transplantation. Previously, we reported the success of constructing glomerular epithelial cells for removal
of immune complex, in which complement receptor of type 1 (CR1) was over-expressed on the membrane of renal glomerular epithelial
cells and could bind immune complex of DNA/anti-DNA-antibody to remove immune complex through phagocytosis 1]. Attempting
to apply the CR1-expressing cells to cell therapy and evade immune rejection during cell transplantation, we constructed three
plasmids containing genes encoding a soluble fusion protein of cytolytic T lymphocyte associated antigen-4 (CTLA4Ig) and an
enhanced green fluorescent protein (EGFP). The plasmids were transfected to the above-mentioned glomerular epithelial cells
to express both genes simultaneously. Using the clone cells for cell transplantation showed that mice with autoimmune disease
prolonged their life significantly as compared with the control mice, and two injections of the cells at the beginning of
two weeks resulted in remarkable survivability, whereas it requires half a year and 50 administrations of proteins purified
from the same amount of cells to achieve the same effect. |
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Keywords: | cell therapy cell transplantation immune tolerance CTLA4Ig GFP CD28 CD80/86 |
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