Regeneration of hyaline articular cartilage with irradiated transforming growth factor β1-producing fibroblasts

Title
Regeneration of hyaline articular cartilage with irradiated transforming growth factor β1-producing fibroblasts
Authors
Oh, I.S.; Suh, J.K.; Hong, Y.J.; Han, J.U; Song, S.U.
Keywords
JOINT SURFACES, ISOLATED EPIPHYSEAL
Issue Date
2004-05
Publisher
MARY ANN LIEBERT INC PUBL
Abstract
The regeneration of hyaline articular cartilage by cell-mediated gene therapy using transforming growth factor beta(1) (TGF-beta(1))-producing fibroblasts (NIH 3T3-TGF-beta(1)) has been reported previously. In this study, we investigated whether TGF-beta(1)-producing fibroblasts irradiated with a lethal dose of gamma radiation are still capable of inducing the regeneration of hyaline articular cartilage. NIH 3T3-TGF-beta(1) fibroblasts were exposed to doses of 20, 40, or 80 Gy, using a gamma irradiator, and then injected into artificially made partial defects on the femoral condyle of rabbit knee joints. The rabbits were killed 3 or 6 weeks postinjection and hyaline articular cartilage regeneration was evaluated by histological and immunohistochemical staining (n=5 per each group). Irradiated NIH 3T3-TGF-beta(1) fibroblasts started to die rapidly 3 days after irradiation; moreover, the kinetics of their viability were similar regardless of the radiation intensity. TGF-beta(1) expression, measured by ELISA, showed that the TGF-beta(1) protein produced from the irradiated cells peaked 5 days after irradiation and thereafter declined rapidly. Complete filling of the defect with reparative tissue occurred in all the groups, although variations were observed in terms of the nature of the repair tissue. Histological and immunohistochemical staining of the repair tissue showed that the tissue newly formed by irradiated NIH 3T3-TGF-beta(1) fibroblasts after exposure to 20 Gy had hyaline cartilage-like characteristics, as was observed in the nonirradiated controls. On the other hand, the repair tissue formed by NIH 3T3-TGF-beta(1) fibroblasts irradiated with 40 or 80 Gy showed more fibrous cartilage-like tissue. These results suggest that TGF-beta(1)-producing fibroblasts irradiated up to a certain level of lethal dose (i.e., 20 Gy) are able to induce normal-appearing articular cartilage in vivo. Therefore, irradiated heterologous cell-mediated TGF-beta(1) gene therapy may be clinically useful and an efficient method of regenerating hyaline articular cartilage.
URI
http://dspace.inha.ac.kr/handle/10505/20397
ISSN
1076-3279
Appears in Collections:
Medical School/College of Medicine (의학전문대학원/의과대학) > Medical Science (의학) > Journal Papers, Reports(의학 논문, 보고서)
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