Menisci are efficiently transduced by recombinant adeno-associated virus vectors in vitro and in vivo.

Background: Meniscal tears remain an unsolved problem in sports medicine. Gene transfer is a potential approach to enhancing meniscal repair. Recombinant adeno-associated virus is a method of gene transfer that has advantages over previously used approaches to this problem.

[Conservative treatment of knee osteoarthritis].

The management of knee osteoarthritis requires a combination of both non-pharmacological and pharmacological treatment modalities. Non-pharmacological therapies include patient education, lifestyle modification, weight reduction, regular exercise, physiotherapy and the use of orthopaedic appliances (canes, insoles, braces). Pharmacological treatment includes the application of non-opioid or opioid analgetics, non-steroidal anti-inflammatory drugs or coxibes and intra-articular glucocorticoids.

Replicative multivirus infection with cytomegalovirus, herpes simplex virus 1, and parvovirus B19, and latent Epstein-Barr virus infection in the synovial tissue of a psoriatic arthritis patient.

Background: Psoriatic arthropathy occurs as complicating feature in about 5-7% of psoriasis patients. Infectious mechanisms including viral antigens have been suggested by serologic data as CD8 T cellular specifity towards viral epitopes.

Objective And Results: We here reported a case of a 32-year-old male psoriatic arthritis patient, where we could demonstrate simultaneous infection with cytomegalovirus (CMV), herpes simplex virus type I (HSV1) and parvovirus B19 (B19), as well as latent Epstein-Barr virus (EBV) infection within the synovial tissue by immunohistochemistry (CMV, parvovirus B19, HSV1, EBV-LMP) and DNA-in situ-hybridization (CMV).

Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation.

Background: Genetically engineered chondrocytes could be used to enhance cartilage repair. Fibroblast growth factor 2 (FGF-2) is a mitogen for chondrocytes and may be a candidate for gene transfer approaches to stimulate chondrocyte proliferation. In the present study, we tested the hypothesis that human FGF-2 (hFGF-2) gene transfer into articular chondrocytes modulates cell proliferation in an ex vivo model of chondrocyte transplantation.

Parvovirus B19-related chronic monoarthritis: immunohistochemical detection of virus-positive lymphocytes within the synovial tissue compartment: two reported cases.

Apart from systemic symptoms of viral infection parvovirus B19, the infectious agent in erythema infectiosum, can lead to mainly self-limited acute and chronic arthropathy. Because mild subclinical features of the disease can be easily overlooked, joint affections might appear as isolated symptoms. We here report two cases of chronic monoarthritic symptoms of unknown origin, where immunohistochemical detection of B19-positive lymphocytic cells in the synovial tissue led to the diagnosis of B19 arthropathy.

Sustained transgene expression in cartilage defects in vivo after transplantation of articular chondrocytes modified by lipid-mediated gene transfer in a gel suspension delivery system.

Background: Genetically modified chondrocytes may be able to modulate articular cartilage repair. To date, transplantation of modified chondrocytes into cartilage defects has been restricted to viral vectors. We tested the hypothesis that a recombinant gene can be delivered to sites of cartilage damage in vivo using chondrocytes transfected by a lipid-mediated gene transfer method.

Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage.

Successful gene transfer into articular cartilage is a prerequisite for gene therapy of articular joint disorders. In the present study we tested the hypothesis that recombinant adeno-associated virus (rAAV) vectors are capable of effecting gene transfer in isolated articular chondrocytes in vitro, articular cartilage tissue in vitro, and sites of articular damage in vivo. Using an rAAV vector carrying the Escherichia coli beta-galactosidase gene (lacZ) under the control of the cytomegalovirus (CMV) immediate-early promoter/enhancer (rAAV-lacZ), transduction efficiency exceeded 70% for isolated normal human adult articular chondrocytes, and osteoarthritic human articular chondrocytes.

[Gene transfer in cruciate ligament surgery. Natural science-based principles and possible clinical applications].

Current challenges in anterior cruciate ligament surgery include graft remodeling and tendon-to-bone healing. The development over the past few decades of methods for delivering genes to musculoskeletal tissues has stimulated interest in its application for orthopedic problems, including anterior cruciate ligament surgery. Despite substantial progress, a number of technical issues need to be addressed before gene transfer might be considered as an approach to improve the structural and functional properties of anterior cruciate ligament grafts.

Gene transfer of a human insulin-like growth factor I cDNA enhances tissue engineering of cartilage.

The repair of articular cartilage lesions remains a clinical problem. Two novel approaches to cartilage formation, gene transfer and tissue engineering, have been limited by short-term transgene expression in transplanted chondrocytes and inability to deliver regulatory signals to engineered tissues according to specific temporal and spatial patterns. We tested the hypothesis that the transfer of a cDNA encoding the human insulin-like growth factor I (IGF-I) can provide sustained gene expression in cell-polymer constructs in vitro and in vivo and enhance the structural and functional properties of tissue-engineered cartilage.

Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation.

Articular cartilage, the tissue that forms the gliding surface of joints, has a poor regenerative capacity. Insulin-like growth factor-I (IGF-I) is a polypeptide that is anabolic and mitogenic for cartilage. Transfection of articular chondrocytes with an expression plasmid vector containing the cDNA for human IGF-I under the control of the cytomegalovirus promoter/enhancer led to expression of the transgene and synthesis of biologically relevant amounts of IGF-I protein.

Efficacy of cationic liposome-mediated gene transfer to mesangial cells in vitro and in vivo.

Mesangial cells represent a major target for gene transfer approaches to the kidney. To establish a liposome-based system for transfection of mesangial cells we analyzed the efficacy and toxicity of different cationic liposomes and other nonviral transfection methods in primary cultures of rat and human mesangial cells using the Escherichia coli beta-galactosidase (lacZ) gene as a marker. In addition, an expression vector containing a human renin cDNA under the control of the cytomegalovirus immediate-early promoter/enhancer was generated, introduced into mesangial cells, and assayed in a system of transient gene expression.

Efficient lipid-mediated gene transfer to articular chondrocytes.

We examined nonviral, lipid-mediated gene transfer methods as potential tools for efficient transfection of articular chondrocytes. Transfection conditions were determined for primary cultures of normal human articular, osteoarthritic human articular and normal bovine articular chondrocytes using a lacZ reporter gene construct with the commercially available cationic liposomes Cellfectin, DMRIE-C, LipofectAmine, Lipofectin, LipoTaxi, TransFast and the lipid-based reagent FuGENE 6. Optimized conditions were then evaluated in an ex vivo model of chondrocyte transplantation.

In vivo gene transfer: focus on the kidney.

Renal gene transfer techniques are being developed as a novel experimental approach to understand the pathogenesis of renal disease and to potentially develop new therapeutic tools. We review the currently available technology to introduce foreign genetic material into renal tissue, i.e.

Analysis of lectin binding sites in the gut of hooded Lister rats with special emphasis on recently detected lectins.

Seven recently isolated lectins were tested for their ability to bind to tissue sections of rat gut. Binding sites for N-Acetylgalactosamine specific lectins were found in mucins, in the brush border membrane and in goblet cells. Non-reducing terminal mannose residues were absent from cell surface membranes but were detected in the supranuclear region of goblet cells and enterocytes.