Mesenchymal stem cells (MSC) display unique suppressive properties on T-cell immunity, thus representing an attractive vehicle for the treatment of conditions associated with harmful T-cell responses such as organ-specific autoimmunity and graft-versus-host disease. Toll-like receptors (TLR) are primarily expressed on antigen-presenting cells and recognize conserved pathogen-derived components. Ligation of TLR activates multiple innate and adaptive immune response pathways to eliminate and protect against invading pathogens. In this work, we show that TLR expressed on human bone marrow-derived MSC enhanced the immunosuppressive phenotype of MSC. Immunosuppression mediated by TLR was dependent on the production of immunosuppressive kynurenines by the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase-1 (IDO1). Induction of IDO1 by TLR involved an autocrine interferon (IFN)-b signaling loop, which was dependent on protein kinase R (PKR), but independent of IFN-c. These data define a new role for TLR in MSC immunobiology, which is to augment the immunosuppressive properties of MSC in the absence of IFN-c rather than inducing proinflammatory immune response pathways. PKR and IFN-b play a central, previously unidentified role in orchestrating the production of immunosuppressive kynurenines by MSC. STEM CELLS 2009;27:909-919 Disclosure of potential conflicts of interest is found at the end of this article.
Meniscus tears are frequent indications for arthroscopic evaluation which can result in partial or total meniscectomy. Allografts or synthetic meniscus scaffolds have been used with varying success to prevent early degenerative joint disease in these cases. Problems related to reduced initial and long-term stability, as well as immunological reactions prevent widespread clinical use so far. Therefore, the aim of this study was to develop a new construct for tissue engineering of the human meniscus based on an acellular meniscus allograft. Human menisci (n = 16) were collected and acellularized using the detergent sodium dodecyl sulfate as the main ingredient or left untreated as control group. These acellularized menisci were characterized biomechanically using a repetitive ball indentation test (Stiffness N/mm, residual force N, relative compression force N) and by histological (hematoxylin-eosin, phase-contrast) as well as immunohistochemical (collagen I, II, VI) investigation. The processed menisci histologically appeared cell-free and had biomechanical properties similar to the intact meniscus samples (p > 0.05). The collagen fiber arrangement was not altered, according to phase-contrast microscopy and immunohistochemical labeling. The removal of the immunogenic cell components combined with the preservation of the mechanically relevant parts of the extracellular matrix could make these scaffolds ideal implants for future tissue engineering of the meniscus.
Hallux valgus deformity is a very common pathological condition which commonly produces painful disability. It is characterised as a combined deformity with a malpositioning of the first metatarsophalangeal joint caused by a lateral deviation of the great toe and a medial deviation of the first metatarsal bone.Taking the patient’s history and a thorough physical examination are important steps. Anteroposterior and lateral weight-bearing radiographs of the entire foot are crucial for adequate assessment in the treatment of hallux valgus.Non-operative treatment of the hallux valgus cannot correct the deformity. However, insoles and physiotherapy in combination with good footwear can help to control the symptoms.There are many operative techniques for hallux valgus correction. The decision on which surgical technique is used depends on the degree of deformity, the extent of degenerative changes of the first metatarsophalangeal joint and the shape and size of the metatarsal bone and phalangeal deviation. The role of stability of the first tarsometatarsal joint is controversial.Surgical techniques include the modified McBride procedure, distal metatarsal osteotomies, metatarsal shaft osteotomies, the Akin osteotomy, proximal metatarsal osteotomies, the modified Lapidus fusion and the hallux joint fusion. Recently, minimally invasive percutaneous techniques have gained importance and are currently being evaluated more scientifically.Hallux valgus correction is followed by corrective dressings of the great toe post-operatively. Depending on the procedure, partial or full weight-bearing in a post-operative shoe or cast immobilisation is advised. Post-operative radiographs are taken in regular intervals until osseous healing is achieved.Cite this article: Fraissler L, Konrads C, Hoberg M, Rudert M, Walcher M. Treatment of hallux valgus deformity. EFORT Open Rev 2016;1:295-302. DOI: 10.1302/2058-5241.1.000005.
Parallel to the rising number of revision hip procedures, an increasing number of complex periprosthetic osseous defects can be expected. Stable long-term fixation of the revision implant remains the ultimate goal of the surgical protocol. Within this context, an elaborate preoperative planning process including anticipation of the periacetabular defect form and size and analysis of the remaining supporting osseous elements are essential. However, detection and evaluation of periacetabular bone defects using an unsystematic analysis of plain anteroposterior radiographs of the pelvis is in many cases difficult. Therefore, periacetabular bone defect classification schemes such as the Paprosky system have been introduced that use standardized radiographic criteria to better anticipate the intraoperative reality. Recent studies were able to demonstrate that larger defects are often underestimated when using the Paprosky classification and that the intra- and interobserver reliability of the system is low. This makes it hard to compare results in terms of defects being studied. Novel software tools that are based on the analysis of CT data may provide an opportunity to overcome the limitations of native radiographic defect analysis. In the following article we discuss potential benefits of these novel instruments against the background of the obvious limitations of the currently used native radiographic defect analysis.
Attachment of SF to LM-111 by itself has only minor effects on the expression of MMP-1 or MMP-3, but it facilitates the TGFbeta-induced expression of MMP-3 significantly. This mode of MMP-3 induction may therefore contribute to inflammatory joint destruction in RA independent of the proinflammatory cytokines interleukin (IL)1beta or tumour necrosis factor (TNF)alpha.
There is no difference in the outcome between the three tested matrices in the treatment of osteochondral defects in the rabbit knee. The results of this in vitro experiment are promising and with refinement may lead to useful clinical therapies.
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