characterized by the formation of hyaline or myxoid cartilage and the presence of chondrocytic cells. Benign cartilage tumors are much more common than malignant ones. Benign tumors include osteochondroma, enchondromas, chondroblastoma, juxtacortical chondroma, and chondromyxoid fibroma, and malignant tumors chondrosarcomas. Chondrosarcoma can be subdivided into peripheral-m, dedifferentiated-, mesenchymal-, and clear cell chondrosarcoma. The clinical presentation of these tumors differs for age group, gender, and site. Benign tumors arise primarily in the younger age group and mostly as single lesions. However, in rare hereditary syndromes, they can be found in multiple skeletal locations. In comparison, malignant cartilaginous tumors are the second-largest group of primary bone tumors. A majority of them occur in previously normal bone; however, some arise from preexisting benign tumors. Most chondrosarcoma are solitary, but they can present as multiple lesions in patients with hereditary syndromes.
Although ongoing, stem cell therapy is being evaluated as a means to regenerate cartilage in patients with cartilage removal along with tumor extraction. Researchers from numerous universities are extracting mesenchymal stem cells derived from allogenic umbilical cord. The stem cells are mixed with a scaffold such as hyaluronan, and clinical trials are being conducted to study the effect of this protocol in patients with previous cartilage removal/loss. Identification of growth factors that help one’s body repair lost cartilage and activate transplanted stems cells in regenerating cartilage is a key area of research.
Tendons
Tendons are dense connective tissues that connect muscles to bone. The connective tissue merges with the periosteum at the insertion point and is a movable attachment. At the origin, it merges with the fascia and this point determines the tendon’s function. Tendons are relatively poorly vascularized and do not heal well when injured.
Tendinitis
Tendinitis refers to the inflammation of the tendon tissue, which involves larger-scale acute injuries. Injuries are more common in the upper and lower limbs as compared to the hips and torso. Variation in frequency and severity of tendinitis depends on the type, frequency, and severity of the use. Inflammation of the Achilles tendon is the most common site of injury, especially in sports that involve lower-limb stress. Patellar tendinitis is common in basketball and volleyball players because these sports involve jumping and landing. Symptoms include pain, joint stiffness, burning surrounding the entire joint with erythema, and possible visible knots. The pain usually worsens after strenuous activity, and the tendon can become stiff the following day. If the symptoms last several months, tendinosis has to be ruled out.
Tendinosis
Tendinosis, or chronic tendon injury, results due to tendon damage at a cellular level. It is caused by micro-tears in the connective tissue, leading to an increase in tendon repair cells in and around the tendon. This reduces the tensile strength, thereby increasing the chance of tendon rupture. Characteristics of tendinosis include degenerative changes in the collagenous matrix, hypercellularity, hypervascularity, and a lack of inflammatory cells. Symptoms resemble tendinitis features, with the increased water content and disorganized collagen matrix detected by ultrasonography or magnetic resonance imaging (MRI).
Tendon bioengineering
Researchers are investigating nonsurgical care for tendon damage using mesenchymal stem cells. Similar to stem cells and scaffolding used in ligament reconstruction, stem cells derived from bone marrow or adipose are being engineered to seed repair of damaged tendons. Successful animal models have followed through with this procedure using mesenchymal stem cells derived from horse’s bone marrow and transplantation in the bowed tendon.
Ligaments
Ligaments are dense collagenous tissue that join bones and play a significant role in musculoskeletal biomechanics. They are formed through the excretion of collagen and elastin by fibroblasts and are intercellular connective tissue with very few cells, blood vessels, and nerves. They represent an important area of orthopedic treatment with a great many challenges to restore normal mechanical function.
Inflammation
Ligaments are poorly vascularized and dense structures, and therefore an inflammatory condition can be extensively damaging. An inflammatory response is initiated when the tissue is subjected to stress. The stress can be in the form of repetitive loading of the ligament, within its physiological limits, over an extended period of time. This causes micro-damage within the collagen fibers and can trigger an inflammatory response. On the other hand, when physical activity presents, a sudden overload on the ligament causes a distinct inflammatory response. In this case, healing does not result in full recovery of the functional properties of the tissue. Chronic inflammation can occur when the ligament tissue is not allowed to rest, heal, or recover. Prolonged exposure to loading of the ligament over a long period of time without sufficient rest and recovery also causes cumulative micro-damage.
Infection
Infections can affect ligaments either through internal inflammation or directly through wounds. Internal infections such as necrotizing fasciitis and bone infections can affect and pose a significant threat to the ligaments. Direct infections of the ligaments are uncommon but can occur when there is an open wound in proximity to the structure.
Other diseases
Several other diseases, including autoimmune conditions, can involve ligaments. Autoimmune diseases such as rheumatoid arthritis (RA), mixed connective tissue diseases, polychondritis, systemic lupus erythematosus (SLE), and scleroderma can involve the ligaments either through the normal inflammatory process or by causing dysfunction of the joints. Other diseases include tendinitis, fibromyalgia, and osteroarthritis.
Injury or rupture
When a ligament is overstretched or torn, it is called a sprain. When separated from the attached bone, it is called an avulsion. Most injuries or ruptures are caused by accidents or sports-related activities and result due to use of a joint beyond its physiological range of motion. Repetitive stress can also cause injury by weakening the ligament and making it more susceptible to damage under physiological conditions. In general, when ligament damage occurs beyond repair (rupture or injury), a healthy ligament is used to reconstruct the damaged one. Although this protocol is mostly successful, it is associated with postoperative pain and loss of function at the donor site. Therefore, stem cells isolated from bone marrow are being used to engineer ligaments that would be used to stabilize a joint and avoid the effects of donor site dysfunction.
Ayesha Irum
Muhammad Saad Faiz
Army Medical College, National University of Sciences and Technology
See Also: Cancer Stem Cells: Overview; Cartilage, Tendons, and Ligaments: Current Research on Isolation or Production of Therapeutic Cells; Cartilage, Tendons, and Ligaments: Stem and Progenitor Cells in Adults.
Further Readings
Boon, Nicholas A., et al. Davidson’s Principles and Practice of Medicine. New Delhi: Elsevier, 2006.
Colorado Stem Cell Treatment Center. “Auto-Immune Diseases.” http://www.healingcell.com/medical-conditions/auto-immune-diseases
