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Transduction of anti-cell death protein FNK suppresses graft degeneration after autologous cylindrical osteochondral transplantation.

ABSTRACT: This study shows that artificial super antiapoptotic FNK protein fused with a protein transduction domain (PTD-FNK) maintains the quality of osteochondral transplant by preventing chondrocyte death. Cylindrical osteochondral grafts were obtained from enhanced green fluorescent protein (EGFP)-expressing transgenic rats, in which living chondrocytes express green fluorescence, and submerged into medium containing PTD-FNK, followed by transplantation into cartilage defects of wild-type rats by impact insertion simulating autologous transplantation. The tissues were histologically evaluated by hematoxylin-eosin and Safranin-O staining. At 1 week, chondrocyte alignment was normal in the PTD-FNK treatment group, whereas all grafts without PTD-FNK treatment showed mixed cluster cell distribution. At 4 weeks, all grafts with PTD-FNK treatment showed almost normal matrix, whereas two grafts without PTD-FNK treatment showed fibrocartilage. Notably, all grafts with PTD-FNK retained high intensity of Safranin-O staining, but all grafts without PTD-FNK largely lost Safranin-O staining. PTD-FNK significantly suppressed a decrease in the survival rate and the density of EGFP-positive cells at 1 and 2 weeks, and this tendency continued at 4 weeks. The results of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-nick end-labeling staining showed that PTD-FNK inhibited cell death, indicating that PTD-FNK protects chondrocyte death and suppresses graft degeneration.

SUBMITTER: Nakachi N

PROVIDER: S-EPMC2664932 | biostudies-other | 2009 Mar

REPOSITORIES: biostudies-other

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Project description:Osteochondral defects of the knee are common in orthopaedic patients. They are challenging to treat, especially in young, highly demanding patients who do not qualify for arthroplasty. Among the many possibilities to treat osteochondral lesions presented so far, none is ideal. Because of the poor healing potential of cartilage, treatment outcomes significantly worsen with larger lesions. The treatment of large defects usually requires expensive solutions, sometimes including second-stage surgery. Using mesenchymal stem cell transplantation and cancellous bone autografts, the technique presented here for osteochondral lesion reconstruction can be effectively used to treat large osteochondral lesions in a single-stage procedure. Technique Video Video 1 Osteochondral lesion reconstruction using mesenchymal stem cell transplantation and cancellous bone autografts; right knee. Patients are considered candidates after careful selection. To promote mesenchymal stem cell growth, 4 days before surgery, patients are administered granulocyte colony-stimulating factor. On the day of surgery, the mesenchymal stem cell suspension is obtained, using an MSC blood separator, under the control of the blood bank. A cytometric test is performed for the quantitative evaluation of cell lines, as well as a histopathological evaluation of stained preparations. The cell suspension is then transferred to the operating theater. The diagnosis is confirmed arthroscopically through a standard anterolateral portal, and concomitant lesions are excluded. Mini-open access is created next to the site of the lesion. After the lesion is exposed, delaminated cartilage or bony-cartilage sequestrum is removed. Using a bone spoon, the bony edges of the cavity are resected to healthy cartilaginous tissue. The next step is decortication and debridement of the bottom. To ensure the integration of bone grafts, it is necessary to remove the sclerotic subchondral bone layer until bleeding from the bone occurs. An additional factor improving the blood supply is the microfracturing the bottom of the cavity. From a separate site above the iliac crest, autologous cancellous bone grafts are harvested. The bottom of the lesion is filled with the debris of the cancellous bone. Restoration with a bone graft is performed up to the height of the surrounding healthy bone margin. During this time, the previously sized collagen sponge Tachosil is soaked in MSC suspension. The sponge is placed on the lesion and adjusted to the edges of the lesion using tweezers. The soaked implant should not cover surrounding healthy cartilage edges, but only fill the cavity. The entirety of the damaged fragment is covered with a 2-component fibrin glue. After binding, a suspension of mesenchymal cells, is administered under the fibrin layer using a no. 12 needle, and the application site is sealed with the rest of the glue. The wound is closed with layered sutures and sealed with sterile dressing. The operated joint is protected by cocoon dressing to limit mobility in the early postoperative period.

Project description:INTRODUCTION:Large cystic osteochondral lesions of the talus (OLTs) have been shown to have inferior clinical outcomes after reparative techniques such as bone marrow stimulation. Autologous osteochondral transplantation has been viewed as an alternative choice for treating these lesions, but donor-site morbidity has limited its application. Excellent clinical outcomes have been shown in repairing these types of lesions with autologous osteoperiosteal grafts, and these outcomes are achieved at a low cost and without donor-site morbidity in the normal knee joint. This will be the first randomised controlled trial to compare the two surgical techniques, and recommendations for the treatment of patients with large cystic OLTs will be provided. METHODS AND ANALYSIS:A non-inferiority randomised controlled trial will be conducted. A total of 70 participants with clinically diagnosed large cystic OLTs will be randomly allocated to either the experimental group or the control group at a ratio of 1:1. The experimental group will be treated with autologous osteoperiosteal cylinder graft transplantation, while the control group will be treated with autologous osteochondral transplantation. The primary outcome measure will be the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Score and the Short Form 12 (SF-12) questionnaire. Secondary outcome measures will include the secondary arthroscopy International Cartilage Repair Society score, the Magnetic Resonance Observation of Cartilage Repair Tissue score, the Tegner activity level score, the visual analogue scale, routine X-rays, CT and complications. These parameters will be evaluated preoperatively, as well as at 3, 6, 12, 24, 36 and 60 months postoperatively. In this trial, we hypothesised that both procedures offer good results for the treatment of patients with large cystic OLTs, and occurrence of donor-site morbidity in autologous osteoperiosteal cylinder graft transplantation group is less than that in autologous osteochondral transplantation group. ETHICS AND DISSEMINATION:The current study was approved by the board of research ethics of Peking University Third Hospital Medical Science Research Ethics Committee. The results of this study will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER:NCT03347877.

Project description:BackgroundThe treatment of large osteochondral lesions of the talus (OLTs) is challenging due to the poor intrinsic reparative capability of the damaged articular cartilage. Autologous transfer of bone and periosteum has been used successfully in the treatment of large defects in animals, and therefore it was believed that this technique might show similar results in humans. The purpose of this study was to assess the outcome of an innovative technique for autologous transplantation of cancellous tibial graft with periosteal transfer in large OLTs.MethodsForty-one patients (22 females, 19 males), with a mean age of 34.9 years (range, 18-72 years), with a large OLT (>200 mm2) were treated with autologous bone graft and periosteum transfer. OLTs averaging 310 mm2 were identified on a preoperative computed tomography scan. The procedure consisted of malleolar osteotomy, curettage of sclerotic bone, autologous bone graft from the proximal tibia, and transfixion of periosteum over the graft. Outcome measures, including the pain visual analog scale (VAS), ankle range of motion (ROM), American Orthopaedic Foot & Ankle Society (AOFAS) score, and Foot & Ankle Disability Index (FADI), were compared between preoperative and 1 and 2 years following surgery.ResultsThere were significant improvements in VAS pain score from 7.7 before surgery to 1.1 at 1 year after surgery and 0.4 at 2 years or more after surgery. The AOFAS and FADI scores were also significantly improved from 40.3 and 53.3 preoperatively to 95 and 93.2 postoperatively at 1 year and 95 and 93.2 at 2 or more years postoperatively, respectively. Postoperative complications included 2 patients who required removal of medial malleolar osteotomy tension bands due to symptomatic hardware. There were no nonunions or malunions of the osteotomies and no donor site complications.ConclusionAutologous bone graft and periosteum transfer was an effective treatment for large OLTs leading to significant decreases in pain and improvement in functional scores at more than 2 years after surgery.Level of evidenceLevel IV, retrospective case series.

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Transduction of anti-cell death protein FNK suppresses graft degeneration after autologous cylindrical osteochondral transplantation.

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