Current Rheumatology Reviews - Volume 5, Issue 1, 2009

Injured articular cartilage has a limited capacity for self-repair. This feature is greatly exacerbated with aging due to the progressive decrease in physiological capacity and reduced ability to respond to environment stress [1,2]. Injuries usually result in the development of degenerative changes, ultimately leading to osteoarthritis (OA) that affects the articular joints of 15% of the US population [3]. There is an increasing need for the development of biologically based approaches for cartilage repair. The ultimate aim is to repair the damaged cartilage tissue with new functional tissue using living cells (alone or in combination with suitable scaffolds) that will integrate with the patient's remaining tissue and yield a regenerated functional joint, which could continue to repair itself and maintain tissue homeostasis, and remain functional throughout the life of the patient. Most of the present treatment modalities are directed towards the alleviation of symptoms rather than cure. There are promises in the application of mesenchymal stem cells (MSC) therapy in the treatment of osteoarthritis and cartilage repair. The goal of the special edition is to review some of the recent advances the use of stem cells in cartilage repair and regeneration. Osteoarthritis: The Need for Innovative Therapeutic Interventions (Ann K. Rosenthal) Osteoarthritis is the most common form of arthritis in adults and is projected to increase in prevalence as the population ages. This review summarizes the currently available management strategies for osteoarthritis, the rationale behind their use and the current data supporting their efficacy. It underscores the need for new and effective therapies for this common and disabling condition.

Osteoarthritis is the most common form of arthritis in adults and is projected to increase in prevalence as the population ages. This review summarizes the currently available management strategies for osteoarthritis, the rationale behind their use, and the current data supporting their efficacy. It underscores the need for new and effective therapies for this common and disabling condition.

Cellular-based therapies for cartilage tissue engineering have evolved quite significantly in the past decades. The realization that such an endeavor requires the acquisition of an adequate stem or progenitor cell population, techniques to effectively maintain or induce the desired phenotype and efficient culturing and implantation conditions have led researchers to develop a wide variety of protocols to approach the issue. Originally, cells taken from donor grafts of healthy cartilage were used as the cell source for tissue engineering constructs. Since then, however, researchers have moved on to cells from the adipose tissue, embryonic tissues, bone marrow and other sources. Similarly, as the potential for different cell sources to generate functional mesenchymal lineage tissues are discovered, several differentiation and phenotypic maintainance stimuli have been explored to optimize the resulting grafts. Physical stimuli in the form of mechanical compression as well as chemical stimuli in the form of growth factor cocktails have all proven effective in the induction of cells into the chondrogenic lineage to varying degrees. Finally, substrate expansion of these cells in materials ranging from naturally occuring ploymers such as fibrin, to synthetic and micro-fabricated structures is an active field of research. This review will discuss the most recent methods being utilized for the initiation of chondrogenesis from various stem cell sources as well as some methods being explored in our laboratory.

Injured cartilage tissue has a limited capacity to heal. There is increasing need for the development of biologically based approaches for cartilage repair. The ultimate aim is to repair the damaged cartilage tissue with new functional tissue using living cells (alone or in combination with suitable scaffolds) that will integrate with the patient's remaining tissue and yield a regenerated functional joint, which could continue to repair itself and maintain tissue homeostasis, and remain functional throughout the life of the patient. Cell therapy approaches represent a novel strategy in the treatment of cartilage diseases. Among the different types of stem/progenitor cells that are currently being evaluated, the benefits and limitations of approaches using embryonic and adult stem cells will ultimately depend on factors related to efficacy and safety. To achieve these goals a clear and profound understanding of the molecular determinants of chondrocyte differentiation and cartilage tissue formation is essential, including the specific effect of trophic factors guiding the chondrogenic differentiation process, their relationship with the tissue microenvironment, and how they translate to an epigenetically stable and homogeneous functional tissue. Despite the increasing progress in the application of human embryonic stem cells for cartilage repair, ethical and safety concerns (primarily teratoma and tumor formation) remain to be resolved. Adult stem cells have demonstrated the greatest promise and bone marrow-derived stromal cell subpopulations represent the most widely studied cell types. Developmentally immature marrow stromal cells have been isolated by several groups which appear capable of meeting most, if not all, of the criteria needed for a successful approach. Here we will review the use of embryonic and adult stem cells for cartilage tissue engineering.

Frustrated by limited availability of cells that are difficult to sustain in culture, investigators have long sought an alternative to chondrocytes for use in generating cells for cartilage repair. This search has led to a comprehensive evaluation of “mesenchymal stem cells”, non-embryonic stem cells recovered in aspirates of bone marrow and other tissues derived from the mesoderm. MSCs indeed possess an avid propensity for chondrogenic differentiation. Marrow and adipose tissue-derived MSCs show promise for generating intact, cellular cartilage in vitro that may be useful for clinical trials. Cultured in diffusion chambers on engineered cellular scaffolds and bio-matrices, these cells allow us to escape the biological and practical limitations that have hindered the development of restorative therapy of osteoarthritis by cartilage and cultured chondrocytes.

The regeneration of damaged cartilage due to injuries and diseases is a major goal for the future. Cartilage has limited healing capacity. There have been a number of studies shown to induce cartilage regeneration both in vitro and in vivo. Yet we are far from obtaining regenerated cartilage that has the properties similar to the native cartilage. Chondrogenesis of mesenchymal stem cells (MSCs) can be induced by biophysical and biochemical factors. This review article focuses on the recent studies and their findings on the role of mechanical loading on inducing chondrogenesis of MSCs. Previous studies have demonstrated promising results on mechanical stimulation of MSC chondrogenesis. More studies are needed to provide optimal conditions for mechanical stimulation of MSC chondrogenesis and a better understanding in mechanisms behind it. Therefore, it will help to develop new strategies for cartilage repair using MSCbased therapies such as cell transplantation and cartilage tissue engineering.

Cartilaginous tissues, such as articular cartilage and intervertebral disc, are avascular tissues, which rely on transport for cellular nutrition. Comprehensive knowledge of transport properties in such tissues is therefore necessary in the understanding of nutritional supply to cells. Furthermore, poor cellular nutrition in cartilaginous tissues is believed to be a primary source of tissue degeneration, which may result in osteoarthritis (OA) or disc degeneration. In this minireview, we present an overview of the current status of the study of transport properties and behavior in cartilaginous tissues. The mechanisms of transport in these tissues, as well as experimental approaches to measuring transport properties and results obtained are discussed. The current status of bioreactors used in cartilage tissue engineering is also presented.

Recent advances in biomaterial development and cellular therapy have offered the possibility of exploring exciting new strategies to engineer cartilage tissue. Both natural and synthetic biomaterials have been used to design a suitable environment for cell support and provide the necessary biological cues to guide cellular behavior towards tissue repair. As with all other areas of tissue engineering, the advances in cartilage repair have been directed towards defining the appropriate organization between scaffold design, cell type and biomolecules. These hybrid-like approaches have enabled the development of tissue engineering scaffolds that are biomimetic and tailored specifically towards cartilage repair. The objective of this review is to highlight a number of current, novel methodologies to engineer cartilage via the use of biomaterials, cellular therapy and stimulating growth factors.

SLE is characterized by overproduction of various types of antibodies. Under certain circumstances, antibodies aiming some of the neoepitopes of the complement system can be seen. Neoepitopes are not present in the native proteins, but they appear after the structural change of the complement system. One of these antibodies binds the activated product C3 called iC3b; however, its possible part in the pathogenesis of a disease is unknown. Some of the antibodies to the component of the complement system are more significant. One of them is the C3 nephritic factor connected with partial lipodystrophy and with a certain form of mesangial glomerulonephritis. This factor also rarely appears in patients with SLE. Another antibody targets the C1 inhibitor and appears in some patients with lymphomas. Anti-C1q antibodies are present in approximately one third of the patients with lupus, who often have high clinical activity of the disease, and particularly, renal involvement. In the presence of high titers of anti C1q antibodies also the levels of C1q and C4 components of the complement system are also usually low. The levels of the C3 component of the complement system are only slightly lowered or sometimes not at all in SLE as already discussed above. However, according to the findings in our study, patients with higher anti-C1q antibodies seem to show the tendency to have lower serum levels of C3. The presence of the anti-C1q antibodies is not limited or specific just for SLE or lupus nephritis. For the first time, they were described in HUVS (Hypocomplementemic Urticar Vasculitis Syndrome), later in Felty´s syndrome, rheumatoid vasculitis, in hepatitis C or in aging population. The association between the presence of anti-C1q antibodies and the consumption of protein in the classic way of complement activation seen in SLE and in HUVS raises the question, whether these antibodies cause or amplify the classic way of complement activation. The alternative theory sees the anti-C1q antibodies as a mere product of this activation itself, which creates the neoepitopes in the molecule C1q.

Behcet's syndrome (BS) is a multisystemic inflammatory disorder characterized by recurrent oral and genital ulcers and ophthalmic alterations, but also involving other systems, including joints, blood vessels, nervous, respiratory and gastrointestinal tracts. Its etiopathogenesis remains unknown, but epidemiologic data suggest an interaction among genetic, immunologic and infectious factors. BS has a worldwide distribution being most frequently seen in the Mediterranean area, Japan and Middle East. In Brazil there are no substantial data regarding its prevalence or incidence. The aim of the present study was to review the main epidemiologic data, clinical features, diagnostic criteria and current treatment of BS.