Autologous chondrocyte implantation in the knee using fibrin.

Autologous chondrocyte implantation (ACI) is widely used to treat symptomatic articular cartilage injury of the knee. Fibrin ACI is a new tissue-engineering technique for the treatment of full-thickness articular cartilage defects, in which autologous chondrocytes are inserted into a three-dimensional scaffold provided by fibrin gel. The objective of this study is to document and compare mean changes in overall clinical scores at both baseline and follow-up. Fibrin ACI was used to treat deep cartilage defects of the femoral condyle in 30 patients. There were 24 men and 6 women with a median age of 35 years (range 15-55) and with a mean defect size of 5.8 cm(2) (range 2.3-12). Clinical and functional knee evaluations were performed using different scoring systems, MRI was performed 24 months postoperatively, and arthroscopy was performed 12 months postoperatively. All patients achieved clinical and functional status improvements following surgery (P < 0.01). The mean scores of the Henderson classification (MRI evaluation) significantly improved from 14.4 to 7 (P = 0.001), and no graft-associated complications were noted. Arthroscopic assessments performed 12 months postoperatively produced nearly normal (grade II) International Cartilage Repair Society scores in 8 of the 10 study patients. Fibrin ACI offers the advantages of technical simplicity, minimal invasiveness, a short surgery time, and easier access to difficult sites than classical ACI. Based on the findings of this clinical pilot study, we conclude that fibrin ACI offers a reliable means of treating articular cartilage defects of the knee.

Clinical and radiological results after modified distal metatarsal osteotomy for hallux valgus.

BACKGROUND: The chevron osteotomy is an acceptable method for correction of mild and moderate hallux valgus, but can result in instability at the osteotomy site. The purpose of this study was to present clinical and radiological results with our modified technique of osteotomy. MATERIALS AND METHODS: We performed a modified technique of distal osteotomy of the first metatarsal on 77 feet of 46 patients with symptomatic hallux valgus; followed up for an average of 52 months. RESULTS: All of the patients experienced satisfactory pain relief and acceptable cosmesis. The mean postoperative reduction in the intermetatarsal angle was 6.5 degrees and of the metatarsophalangeal angle was 23.0 degrees. There was no loss of correction and there was no discrepancy in preoperative and postoperative lengths of the first metatarsal during the followup period. CONCLUSION: We found our modified distal metatarsal osteotomy to be an effective method of correcting hallux valgus.

MR imaging in a child with scurvy: a case report.

Scurvy is very rare disease in industrialized societies. Nevertheless, it still exists in higher risk groups including economically disadvantaged populations with poor nutrition, such as the elderly and chronic alcoholics. The incidence of scurvy in the pediatric population is very low. This study reports a case of scurvy in a 5-year-old girl with cerebral palsy and developmental delay based on MRI findings.

Total knee arthroplasty without patellar resurfacing.

One hundred and eleven total knee replacements without patellar resurfacing were followed-up for a minimum of 48.8 months (range 48.8-108.2 months; average 78.2 months). Evaluation was performed using the Knee Society Clinical Rating System (KS-CRS). Preoperatively, the mean knee score was 34.3 points and the mean function score was 42.2 points. Postoperatively, this knee score improved to a mean of 91.1 points and the function score improved to mean of 89.6 points at the most recent follow-up. There were no significant differences among the knees with mild, moderate, or severe degenerative change to the patella with regard to the preoperative (p=0.83) and postoperative (p=0.39) knee pain score. It seems likely that the postoperative knee pain is not related to the severity of degenerative change to the patella in total knee arthroplasties performed without patellar resurfacing, and none of those patients required patellar resurfacing to achieve knee pain relief.

Hyaline cartilage regeneration using mixed human chondrocytes and transforming growth factor-beta1- producing chondrocytes.

The purpose of this study was to investigate the efficacy of cartilage regeneration when using a mixture of transforming growth factor-beta1 (TGF-beta1)-producing human chondrocytes (hChon-TGF-beta1) and primary human chondrocytes (hChon) ("mixed cells"), compared with either hChon-TGF-beta1 or hChon cells alone. Specifically, mixed cells or hChon cells were first injected intradermally into the backs of immune-deficient nude mice to test the feasibility of cartilage formation in vivo. Both the mixed cells and the hChon-TGF-beta1 cells alone induced cartilage formation in nude mice, whereas hChon cells alone did not. To further test the efficacy of the cells in generating cartilage, an artificially induced partial thickness defect of the femoral condyle of a rabbit knee joint was loaded with hChon-TGF-beta1 cells with or without mixing additional untransduced hChon cells, and hyaline cartilage regeneration was observed at 4 or 6 weeks. The efficiency of complete filling of the defect and the quality of tissue generated after implanting were evaluated on the basis of a histological grading system modified from O'Driscoll et al. (J. Bone Joint Surg. 70A, 595, 1988). Significantly, mixed cells (14.2 +/- 0.9) produced significantly better results than hChon-TGF-beta1 (9.0 +/- 1.7) or hChon (8.0 +/- 1.8) cells alone. Histological and immunohistochemical staining of the newly repaired tissues produced after treatment with either mixed cells or hChon-TGF-beta1 cells alone showed hyaline cartilage- like characteristics. These results suggest that the implantation of mixed cells may be a clinically efficient method of regenerating hyaline articular cartilage.

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.

Regeneration of hyaline articular cartilage with irradiated transforming growth factor beta1-producing fibroblasts.

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 radiation are still capable of inducing the regeneration of hyaline articular cartilage. NIH 3T3TGF-beta(1) fibroblasts were exposed to doses of 20, 40, or 80 Gy, using a 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-TGFbeta(1) fibroblasts started to die rapidly 3 days after irradiation; moreover, the kinetics of their viability were similar regardless of the radiation intensity. TGF-beta1 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.

Hepatocyte growth factor upregulates thymosin beta4 in human umbilical vein endothelial cells.

Hepatocyte growth factor (HGF) is a mesenchymal-derived cytokine. It exerts in vitro a motogenic effect on various target cells, which is displayed either by cell scattering, locomotion, and migration during the wound repair process of cultured cells, or invasiveness through the extracellular matrix. Although it is known that HGF influences the motogenic effect of endothelial cells, the precise effects of HGF during angiogenesis are still poorly understood. To identify genes regulated via HGF signaling in HUVECs, we used the differential display polymerase chain reaction. In this study, thymosin beta4 was found to be differentially expressed in HGF-treated HUVECs compared with control. Data from HPLC profile and induction of MMPs indicate that HGF may affect the biological behavior of HUVECs through a combination of the direct effects of HGF itself and indirect effects mediated via induction of thymosin beta4 in vitro.