Continuous transforming growth factor beta1 secretion by cell-mediated gene therapy maintains chondrocyte redifferentiation.
One of the most important factors in the production of cartilage is transforming growth factor beta1 (TGF-beta1). To obtain sustained release of TGF-beta1, a cell-mediated gene therapy technique was introduced. We infected chondrocytes with a retroviral vector carrying the TGF-beta1 gene. The single clone derivative showed sustained TGF-beta1 secretion. It also showed constitutive type II collagen expression. Whereas the TGF-beta1 protein itself is unable to induce formation of cartilage in vivo, human chondrocytes engineered to express a retroviral vector encoding TGF-beta1 showed cartilage formation in vivo when cells were injected into nude mice intradermally. These data suggest that cell-mediated gene therapy using TGF-beta1 as a transgene would be a promising treatment for osteoarthritis.
Lee
Dug Keun
DK
TissueGene, Gaithersburg, Maryland 20877, USA. dklee@tissuegene.com
Choi
Kyoung Baek
KB
Oh
In Suk
IS
Song
Sun U
SU
Hwang
Sally
S
Lim
Chae-Lyul
CL
Hyun
Jong-Pil
JP
Lee
Hyeon-Youl
HY
Chi
Guang Fan
GF
Yi
Youngsuk
Y
Yip
Vivian
V
Kim
Jeannie
J
Lee
Eun Byul
EB
Noh
Moon Jong
MJ
Lee
Kwan Hee
KH
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D017690:Cell Transplantation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D024043:Collagen Type II / Q000187:drug effects / Q000378:metabolism; D005240:Feasibility Studies; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012190:Retroviridae / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D019076:Transgenes; D014183:Transplantation, Heterologous
D024043:Collagen Type II; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1