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Stem Cell Applications, Tendon and Ligament

LIGAMENT AND TENDON injuries due to traumatic rupture, overuse, and/or inflammatory processes rank as the 15th most prevalent musculoskeletal condition. Tendon injuries comprise 30–50 percent of all sports injuries, and ligament injuries to the knee joint alone occur in 0.2 percent of the general population per year. Of these knee ligament injuries, the anterior cruciate ligament (ACL) are 95,000 per year and medial collateral ligament (MCL) account for 90 percent. These injuries result in tissue that is compromised ultrastructurally, biochemically, and mechanically years after the injury.

Ligaments and tendons are similarly constructed. They are hypovascular, hypocellular, and hyponeuronal bands of dense connective tissue fibers that connect bone to bone and bone to muscle, respectively, to mediate stability of diarthrodial joints and normal musculoskeletal movement. The primary cellular component is the hbroblast, a connective tissue cell that produces collagen, glycosamino—glycan and glycoproteins. During ligament/tendon repair, newly synthesized collagen becomes cross—linked and disorganized, resulting in the formation of scar—like tissue. These regions are usually weaker, larger in cross section, and more compliant elastically, having a higher creep rate viscoelasti—cally than uninjured ligaments and tendons.

Current Treatment Methods

Current therapeutic regimes used to treat ligament/ tendon injury include suturing, grafting, the application of growth factors, and gene transfer/gene therapy. Suturing is necessary for some ligament/ tendon healing because it holds the ruptured ends in close proximity. But the invasive nature of this technique is undesirable, often resulting in more missed work days than a noninvasive, conservative approach. Furthermore, biomechanical outcome is not always improved with suturing (e.g., medial collateral ligaments). Grafting, which is typically used when sutures alone are not a surgical option, removes any irreparable tissue and replaces it with an autograft or allograft. This process is commonly used with torn anterior cruciate ligaments (ACLs), since ligaments inside a synovial capsule heal poorly, if at all. ACL reconstruction techniques with auto—grafts have drawbacks that include additional procedures for tissue harvest and donor site morbidity. Allografts run an increased risk of transmitting diseases, bacterial infections, or immunologically rejecting the transplanted tissue. A different treatment option for ligaments and tendons that will heal entails the use of exogenous growth factors to reduce healing time by augmenting cell migration and proliferation or modulating extracellular matrix components in the injured region. However, full healing capacity or tissue regeneration remains unattainable. Finally, gene therapy relies on viral or nonviral vectors as delivery agents for incorporating foreign DNA into cells to alter protein synthesis or induce expression of therapeutic proteins by the cells. However, healing is a complicated spatial and temporal process that likely cannot be mimicked by one gene during chronic healing. Proper gene delivery of the foreign DNA and the use of viral vectors which pose additional potential health risks, such as mutagenesis, abnormal cell growth, toxicity from overexpression of growth factors, and development of malignancies, likewise create further complications with this procedure. These techniques provide a transient solution to healing, but the long—term success rate is typically lacking. Because of the above limitations to current therapeutic approaches, the use of stem cells has come to the forefront of research.

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