Introduction
Scleroderma, or systemic sclerosis, is a chronic autoimmune disorder that results in the abnormal production of collagen, leading to tissue fibrosis and hardening. This has an adverse impact on the skin, blood vessels, lungs, kidneys, and gastrointestinal tract, and can cause substantial morbidity and mortality. Although conventional therapies have improved, treating scleroderma remains difficult. However, ongoing research on stem cell therapy holds promising prospects for transforming the management of this debilitating disease.
Numerous clinical trials have investigated the effectiveness and safety of stem cell therapy in treating scleroderma. Although the outcomes may differ, overall, these trials have presented promising findings. In a randomized controlled trial called the Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial, autologous hematopoietic stem cell transplantation showcased better results compared to conventional treatment. This included improved long-term survival and enhanced quality of life for individuals with scleroderma.
What Does the Term Scleroderma Mean?
Scleroderma derives its name from the Greek words "sclero" (hard) and "derma" (skin) due to its main feature of skin thickening and hardening. Nonetheless, it is important to recognize that scleroderma is a systemic condition that affects multiple organs and tissues throughout the body. Scleroderma is characterized by an autoimmune response in which the immune system mistakenly targets healthy tissues, causing inflammation and excessive production of collagen—a protein that gives structure to the body. The abnormal accumulation of collagen leads to a gradual thickening and stiffening of the affected tissues. While the exact cause of scleroderma remains unclear, experts speculate that a combination of genetic susceptibility and environmental triggers may contribute to its onset. There are two main types of scleroderma:
-
Localized.
-
Systemic.
Localized scleroderma primarily affects the skin and underlying tissues, and it is usually limited to specific areas of the body, such as the hands, face, or limbs. It is characterized by the presence of thickened patches of skin, often with a shiny appearance. Systemic scleroderma, or systemic sclerosis, is more severe and affects the skin and multiple organs. It is further classified into two subtypes:
-
Limited cutaneous systemic sclerosis.
-
Diffuse cutaneous systemic sclerosis.
Limited cutaneous systemic sclerosis typically involves the skin of the hands, face, and lower arms, associated with a milder disease course. On the other hand, diffuse cutaneous systemic sclerosis affects a larger area of the skin and is often accompanied by more widespread organ involvement. The diagnosis depends on clinical features, physical examination findings, and specific laboratory tests. There is no cure for scleroderma; treatment focuses on managing symptoms, preventing complications, and slowing disease progression. The approach may involve a multidisciplinary team of healthcare professionals, including rheumatologists, dermatologists, pulmonologists, cardiologists, and gastroenterologists.
Treatment options for scleroderma may include medications to alleviate symptoms, such as nonsteroidal anti-inflammatory drugs (NSAIDs) for joint pain and stiffness, immunosuppressive drugs to suppress the immune system's activity, and medications to improve blood circulation. Physical and occupational therapy can help maintain joint mobility and improve overall function. In more severe cases, organ-specific treatments may be necessary to manage complications related to lung, heart, or kidney involvement. Scleroderma is a chronic condition that requires long-term management and regular monitoring. The prognosis varies depending on the subtype and extent of organ involvement. While the disease can be challenging, advancements in research and treatment have improved outcomes for many individuals with scleroderma. Ongoing research aims to understand the underlying mechanisms of the disease and develop targeted therapies.
What Are the Types of Stem Cells Used in Scleroderma Treatment?
Stem cells are a type of cells that are not specialized and have the capacity for self-renewal and differentiation into specific cell types. These cells have the remarkable potential to repair damaged tissues and regulate the immune system, which makes them a promising treatment approach for a range of conditions, including scleroderma.
Hematopoietic Stem Cells (HSCs):
Hematopoietic stem cells (HSCs) are a specific type of stem cell present in the bone marrow and peripheral blood. These cells have the ability to differentiate into different blood cells. HSCs play a vital role in replenishing the blood cell population and preserving the proper functioning of the immune system. In scleroderma treatment, HSC transplantation, also known as hematopoietic stem cell transplantation (HSCT), has shown promise as an immunomodulatory approach. During HSCT, a patient's own or a compatible donor's HSCs are collected and then re-infused back into the patient after high-dose chemotherapy or immunosuppressive treatment. This procedure aims to reset the immune system, halting the autoimmune response responsible for attacking healthy tissues in scleroderma. Studies have demonstrated that HSCT can lead to prolonged remission and decreased disease activity in some patients with severe scleroderma. However, HSCT is a complex procedure with potential risks and side effects, and it is typically reserved for patients with aggressive or life-threatening forms of the disease.
Mesenchymal Stem Cells (MSCs):
Mesenchymal stem cells (MSCs) are multipotent cells derived from umbilical cord tissue. MSCs have gained significant attention in regenerative medicine due to their immunomodulatory and tissue repair capabilities. In the context of scleroderma, MSCs hold promise as a potential therapeutic tool due to their ability to modulate the immune response and regulate inflammation. These cells can suppress the activity of pro-inflammatory immune cells and promote the expansion of regulatory T cells (Tregs). By doing so, MSCs help restore immune system balance and control the autoimmune component of scleroderma.
Moreover, MSCs can also differentiate into different cell types, including fibroblasts. Fibroblasts are essential cells in the process of tissue repair and remodeling. In scleroderma, excessive activation and proliferation of fibroblasts lead to abnormal collagen production and fibrosis. By introducing MSCs into the affected tissues, it is possible to regulate fibroblast function and inhibit the process of fibrosis, potentially slowing down or reversing the progression of the disease. Clinical trials investigating the use of MSCs in scleroderma treatment have shown promising results in reducing skin thickness, improving lung function, and alleviating other disease-related symptoms. However, further research is still needed to optimize the delivery methods, dosages, and long-term safety of MSC-based therapies.
What Are the Mechanisms of Action of Stem Cell Therapy in the Treatment of Scleroderma?
Stem cell therapy for scleroderma aims to promote tissue regeneration. The exact mechanisms by which stem cells exert their therapeutic effects are still under investigation. However, some proposed mechanisms include:
Immunomodulation:
Scleroderma is characterized by an aberrant immune response that targets healthy tissues, but stem cells have the ability to regulate and restore immune system function. Stem cells can modulate the immune response by inhibiting the activity of pro-inflammatory immune cells like T and B cells, which contribute to inflammation and tissue damage in scleroderma. Moreover, stem cells facilitate the expansion and activation of regulatory T cells (Tregs) that help suppress excessive immune responses.
Anti-fibrotic Effects:
Fibrosis, the excessive deposition of collagen and other extracellular matrix components is a hallmark of scleroderma and contributes to the hardening and thickening of affected tissues. Stem cells possess anti-fibrotic properties that can counteract the fibrotic process. By targeting fibroblasts, stem cells help reduce collagen accumulation and prevent further fibrosis. This anti-fibrotic effect can slow down or even reverse the progression of scleroderma by promoting tissue remodeling and improving tissue flexibility.
Angiogenesis Stimulation:
Scleroderma is associated with impaired blood vessel formation, reducing blood supply to the affected tissues. Stem cells secrete various growth factors, cytokines, and chemokines that promote angiogenesis, forming new blood vessels. These include vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Stem cells improve blood circulation by stimulating angiogenesis and enhancing tissue repair processes. Improved angiogenesis can also help alleviate symptoms such as Raynaud's phenomenon, a common manifestation of scleroderma characterized by cold-induced color changes in the fingers and toes due to reduced blood flow.
Apart from their primary functions, stem cells can also exhibit therapeutic effects through paracrine signaling. They have the capability to release various bioactive substances such as growth factors, cytokines, and extracellular vesicles. These molecules have the ability to influence the local cellular environment, leading to processes like tissue regeneration. Stem cell-secreted bioactive molecules can play a role in regulating inflammation, promoting cell survival, stimulating cell growth, and facilitating tissue repair. It is important to note that while the mechanisms described above have been proposed based on preclinical and early clinical studies, further research is still needed to fully elucidate the precise mechanisms so that stem cells exert therapeutic effects in scleroderma. Additionally, the optimal sources, types, and administration methods of stem cells for scleroderma treatment are areas of ongoing investigation.
Conclusion
Stem cell therapy holds tremendous potential for revolutionizing the treatment of scleroderma. By harnessing the immunomodulatory and regenerative properties of stem cells. Despite the promising results, there are challenges to overcome before stem cell therapy becomes the standard treatment for scleroderma. These include standardizing treatment protocols, optimizing cell sources, and ensuring long-term safety. Further research is needed to determine the optimal timing and patient selection for stem cell therapy.
