Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 315

Osteoarthritis (OA) is the most common form of arthritis. It is also called the degenerative joint disease and is one of the 10 most disabling conditions in the developed countries. Osteoarthritis shows a strong positive correlation with aging, with a presentation of bone pain in the elderly. Pathologically, it is an intrinsic disease of cartilage in which biochemical and metabolic alterations in individuals with genetic susceptibility result in its breakdown. Although the term osteoarthritis indicates an inflammatory disease, it is not the predominant feature.

Risk factors for OA include hormonal status, obesity, high bone mineral density, smoking, aging, trauma, joint shape, and usage (occupational or recreational). Twin studies and family studies also show a strong relation to genetics, proving that inheritance is a major factor, particularly in hand and generalized OA along with knee OA. More commonly, a symptomatic condition is experienced by women, except at the hip where men are equally affected.

A variety of mechanical, genetic, and metabolic insults may result in damage of the synovial joints and require repair. In most instances, osteoarthritis appears insidiously, as an aging phenomenon (primary or idiopathic). In these cases, the disease affects few joints but may be generalized. In a small number of cases, osteoarthritis may appear in younger individuals having a predisposing condition such as a previous injury, congenital deformity, or an underlying systemic disorder such as diabetes, hemochromatosis, or marked obesity. In these cases the condition is called secondary osteoarthritis and often involves several joints. Insult to any tissue of the joint (cartilage, bone, capsule, ligament, muscle) causes an impact on the others, resulting in a common phenotype affecting the whole joint.

Often the slow but efficient OA process compensates for the insults, resulting in a pain-free functioning joint. However, due to overwhelming function or poor repair response, it fails (joint failure). The consequential cartilage changes are at the center of the process: (1) there is enzymatic degradation of the major components aggrecan and collagen, (2) the chondrocytes increase their production of matrix components and divide to produce nests of metabolically active cells, and (3) the concentration of aggrecan molecules falls, with an increase in water concentration and swelling pressure of cartilage, further disrupting the type 3 collagen. Thus, the cartilage is vulnerable to load-bearing injury. Cartilage loss is focal and usually restricted to the maximum load-bearing part of the joint.

The extreme burden of OA is aggravated by the insufficiency of current therapies. Pharmacologic and surgical interventions have been used for early cases and when symptoms cannot be controlled with progression of the disease, respectively. Recently, adult mesenchymal stem (MSC) cells, having the ability to differentiate into cells of chondrogenic lineage, have emerged as a treatment with possible great potential. Various varieties of stem cells have shown to differentiate in the presence of appropriate growth stimuli along chondrogenesis pathways.

Stem cells have been isolated from bone marrow and other tissues of mesenchymal origin, such as adipose tissue, placenta, umbilical cord, and amnion. The renewing ability and differentiation potential into chondrocytes has already been documented. Also, the use of mesenchymal cells is not hindered by the availability of healthy cartilage or an intrinsic tendency of the cells to lose their phenotype during expansion. The need for cartilage biopsy is eliminated, thereby avoiding morbidity caused by damage to the donor-site articular surface.

The anti-inflammatory and immunosuppressive properties of stem cells from tissues like bone marrow ensure that cells reduce inflammation in the affected joint. It is hypothesized that the transplanted stem cells can initiate the repair process by differentiating into chondrocytes or by inducing proliferation of the remaining healthy chondroprogenitor cells into mature chondrocytes. In a study by Murphy and colleagues, stem cells isolated by bone marrow tissue were suspended in hyaluronan solution and injected intra-articularly in goats with induced OA. Regeneration of tissue was evident in animals receiving cells in the cartilage area. Similar studies have shown encouraging results and thus it is evident that mesenchymal stem cells embedded on biodegradable scaffold have the potential to be therapeutically effective for conditions such as osteoarthritis.