Introductory Comments on the Need for Innovative Therapies for New and Emerging Diseases
Systemic Lupus Erythematosus (SLE) is a severe and potentially life-threatening autoimmune disease. SLE has a significant impact on the quality of life for patients. SLE patients are afflicted with chronic fatigue, debilitating joint pain, and irreversible organ damage. In addition to symptoms that affect physical health, patients also suffer mental distress due to unpredictable disease flare-ups. SLE illustrates the destruction of the human immune system by attacking its own organs and tissues, resulting in chronic and devastating inflammation. The quality of life for patients with SLE decreases over time and the traditional pharmaceutical approaches available to treat SLE symptoms are inadequate in preventing the progression of the disease. The impact of SLE on patients calls for the introduction of novel approaches. SLE is a disease that researchers in regenerative medicine have devoted their attention in efforts to develop novel methods to combat this devastating disease. Because of the potential to achieve long-term clinical remission, targeted and active Stem Cell therapies for patients with SLE provide an unprecedented opportunity to directly address the underlying cause of autoimmune disorders, and for patients with severe SLE, reset their immune system.
Detailed Explanation of Pathobiology and Mechanisms of the Disease
The pathobiology of SLE is the result of a catastrophic breakdown in peripheral immune system self-tolerance. In patients with SLE, the peripheral B-lymphocytes that self-recognize are activated in an aberrant and exponential fashion, resulting in the production of autoantibodies. The autoantibodies, in conjunction with various nuclear antigens, form immune complexes that have yet to be cleared by the human body. These complexes lead to pathologic deposition in the deep tissues of the body and include, but are not limited to, the kidneys, skin, and synovial membranes, which are further involved in the initiation of inflammatory cascades and complement activation. Once tissues have been flocked by neutrophils and macrophages, proteolytic enzymes and reactive oxygen species are also released and result in profound necrosis. This also leads to a further chronic inflammatory state. Regulatory T (Treg) cells can become numerically and functionally insufficient. This imbalance causes an inability to turn off the immune response to the ongoing attack. This is a major contributor to the chronicity of SLE.
Figure 1: Detailed Explanation of Pathobiology and Mechanisms of the SLE Disease
Historical Approaches to Treatment and Their Major Drawbacks
In the past, generalized immunosuppression was the primary method employed by clinicians when treating severe manifestations of SLE. First-line treatments continue to be prescription oral corticosteroids and more conventional antimalarial agents. When treating more severe cases, where underlying pathology is more detrimental, clinicians tend to employ more aggressive chemical agents, such as cyclophosphamide and mycophenolate mofetil. These approaches essentially do not discriminate between normal and abnormal components of the immune system and are classified as a “brute force” immunosuppression. Such aggressive measures serve to limit more severe manifestations of the disease and serve more to reduce inflammation. Due to the nature of the treatment, real clinical improvements may be more illusionary. For more vulnerable cases, there are real clinical limitations. The prolonged use of corticosteroids leads to a predictable case where corticoid-induced osteoporosis, rapid weight gain, and metabolic syndrome occur. More aggressive treatment protocols using cytotoxic agents significantly increase the daily risk of opportunistic infections and secondary malignancies. The more severe and aggressive treatment protocols lead to the more rapid and aggressive case of treatment resistant disease. This serves as an impetus and a strong rationale to employ more targeted regenerative treatment protocols.
Biological Mechanisms that Provide the Rationale for Preference of Cellular Therapies Over Other Traditional Approaches
The paradigm of the treatment of immunological disorders has been altered by the insertion of specialized Stem Cell groups. Intravenous infusions of mesenchymal Stem Cells have been found to target and effectively treat more aberrant and more destructive immune pathways. Once these cells have been administered to a patient, they have the unique property of being able to migrate to areas of deep tissue inflammation and serve actively as agents of immunomodulation. This process occurs via a mechanism of paracrine signaling and intercellular communication. These cells have the ability to secrete a number of anti-inflammatory cytokines. The bioactive molecules curb the rapid uncontrolled growth of harmful autoreactive T and B lymphocytes. Additionally, the rapid, targeted growth of functional T regulatory lymphocytes through this advanced Stem Cell technology aids in the restoration of the immune system balance and the maturation of dendritic cells. This technology, by fundamentally resetting the microenvironment of the cells, provides the true potential of targeted rheumatic disease remission in patients with Systemic Lupus Erythematosus (SLE) without the use of drugs.
Figure 2: Biological Mechanisms that Provide the Rationale for Preference of Cellular Therapies Over Other Traditional Approaches
Modern methods of advanced regenerative targeted immunological repair provide a rational, safe, and effective alternative. A properly employed Stem Cell procedure targets the essential core mechanisms of the production of autoantibodies and the clearing of immune complexes. As the international clinical research community gains momentum, the delayed hope of many for more precise and resilient medical therapeutics draws closer. The rapid deployment of medical technologies emerging from the research centers in Thailand will likely stimulate positive global response. The complexity of biological cell research combined with effective technologies will provide a medical pathway to permanent health recovery for patients with SLE around the world.