Introduction
Systemic rheumatic diseases like rheumatoid arthritis (RA), lupus (SLE), and systemic sclerosis (SSc) cause inflammation due to problems with the immune system. RA affects joints and tissues, with treatments like targeted drugs, but they may not work for everyone and have risks. SLE is an autoimmune disease with no cure, and current treatments can have side effects. SSc causes skin and organ damage due to immune system issues, and there are limited treatment options. These diseases are hard to treat, so researchers are exploring new therapies like mesenchymal stem or stromal cell (MSC) therapy, which shows promise in restoring immune balance and promoting healing. MSCs can be grown in the lab and given to patients, offering hope for better treatments.
What Are the Characteristics of MSC?
Mesenchymal stem cells (MSCs) were discovered in 1968 and are special cells that can turn into different cell types. They have unique abilities like healing, fighting infections, and calming the immune system. Scientists can find MSCs in various parts of the body, and they can grow a lot of them in the lab. MSCs have been used in many types of research.
In the past, people used "mesenchymal stem cell" and "mesenchymal stromal cell" interchangeably, but now everyone knows that they are different. "Mesenchymal stromal cell" is a better term because it describes their characteristics and therapeutic abilities more accurately. MSCs do not just become different cells; they mainly help by sending signals and controlling the immune system.
MSC therapy is valuable for systemic rheumatic diseases. MSCs have low HLA-II, which means they can be used in different ways. They were first known for fixing tissues and organs, but now it is used to treat chronic inflammatory diseases, too. They release special substances that help damaged tissues heal, and MSCs or these substances can be used to treat injuries.
How Do MSCs Help Regulate the Immune System?
MSCs have the ability to regulate the immune system effectively through their immunomodulatory properties. When it comes to T cells, MSCs have been extensively studied and found to influence them in several ways. They can slow down the growth and activation of T cells, encourage the development of regulatory T cells (Tregs) that dampen immune responses, and promote the transformation of naïve T cells into T helper 2 (Th2) cells, which also have calming effects on the immune system. Furthermore, MSCs reduce the production of inflammatory molecules like interferon (IFN)-γ and tumor necrosis factor α (TNF-α) by T cells while increasing the production of anti-inflammatory cytokines like interleukin (IL)-10.
Regarding B cells, although less is known about MSCs' effects compared to T cells, studies suggest that MSCs can inhibit B cell growth and differentiation, decrease the production of immunoglobulins, and decrease B cell activation and survival. MSCs can also indirectly impact B cells by influencing other immune cells like T cells and dendritic cells.
Additionally, MSCs have the capacity to modify the functioning of macrophages and dendritic cells. They reduce the production of pro-inflammatory cytokines, boost the production of anti-inflammatory cytokines, encourage the development of anti-inflammatory macrophages and regulatory dendritic cells, and limit the phagocytic activity of macrophages.
What Are the Potential Benefits of Using Mesenchymal Stem Cells (MSCs) For Treating Rheumatoid Arthritis(RA)?
Rheumatoid arthritis (RA) is a common inflammatory disease that affects joints and causes pain and damage. Current treatments, like drugs, are effective but do not work for everyone, and the disease often comes back. Researchers are exploring a new treatment using special cells called mesenchymal stem cells (MSCs). These cells can calm down the overactive immune system in RA and prevent further damage to joints. In lab studies and tests on animals, MSCs have shown promise in reducing inflammation and protecting joints. Some small studies in people also suggest that MSCs could help improve RA symptoms and quality of life. However, more research is needed to figure out the best way to use MSCs for RA treatment.
How Do MSCs Control SLE?
Systemic lupus erythematosus (SLE) is a persistent autoimmune disease that impacts the entire body, causing organ dysfunction and significantly affecting the patient's quality of life. It is marked by alternating periods of improvement and worsening. Unfortunately, there is no definitive cure or universally effective treatment for SLE. Although treatments like antimalarial drugs, immunosuppressants, and glucocorticoids are available, they often lead to adverse reactions in patients. Moreover, many individuals with lupus do not respond well to existing therapies. Consequently, there is growing interest in cellular therapies, particularly using MSCs, due to their potential therapeutic benefits in treating SLE.
How Can MSCs Potentially Help Treat Systemic Sclerosis (SSc)?
Systemic sclerosis (SSc) is a disease that affects the whole body and causes problems with the immune system. It damages blood vessels, causes issues with the immune system, and leads to skin and organ scarring. SSc affects many parts of the body, including the lungs, heart, kidneys, and muscles. It can reduce lifespan and quality of life and can be deadly. Current treatments can slow down the disease but do not cure it, and they can have side effects.
Researchers are interested in using special cells called MSCs to treat SSc. MSCs can change the immune system's response, help cells grow, and create new blood vessels. They may also help stop some of the processes that make SSc worse.
What Are the Challenges and Potential Drawbacks of Using MSCs for Treating Systemic Rheumatic Diseases?
The clinical studies mentioned earlier have shown that using MSCs for treating systemic rheumatic diseases is safe and feasible. However, the effectiveness of MSCs in these diseases has varied in clinical trials. Some studies have seen positive results, while others have not shown significant improvement. Several challenges need to be addressed to unlock the full potential of MSC therapy.
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MSCs are not abundant in adult tissues. While they can theoretically be obtained from various parts of the body, the process of collecting them can be invasive and may cause issues like bleeding and infection, especially in the case of bone marrow-derived MSCs. Researchers are exploring alternative sources like nasal turbinate tissue.
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In general, MSCs are considered to have low chances of causing immune reactions. However, when MSCs are grown in large quantities for clinical use, they may become more immunogenic, potentially leading to problems. Additionally, the type of MSCs (autologous from the patient or allogeneic from a donor) can affect their effectiveness. Autologous MSCs from patients with rheumatic diseases may not work as well due to changes in their properties caused by the disease.
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The heterogeneity or variability of MSCs is a major challenge. Factors like the donor's age, sex, health, and genetic makeup, as well as the tissue source and isolation techniques, can all influence the quality and effectiveness of MSCs. Standardizing the manufacturing process is crucial for successful clinical trials.
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MSCs can lose their effectiveness over time, especially with long-term culture. Finding the right cultural methods to maintain their function is important for successful treatments.
Understanding what happens to MSCs after they are injected into the body is crucial. Often, the concentration of MSCs at the target organ is not enough for effective treatment. Researchers are studying different ways to improve MSC migration and survival in target tissues.
MSC-based treatments have shown potential side effects, including:
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Contamination.
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Tumor development.
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Organ fibrosis.
To reduce these risks, rigorous monitoring and comprehensive assessments of the manufacturing process are essential. Some alternative strategies, like using MSC-derived secretomes, are being explored to preserve the benefits of MSC therapy while minimizing these risks.
While MSC-based therapy holds promise for systemic rheumatic diseases, there are limitations and challenges that need to be addressed. Developing standardized protocols and innovative strategies is essential to overcome these hurdles.
How Are Scientists Improving the Use of MSCs for Therapy?
MSCs (mesenchymal stem cells) have been shown to have healing effects. Studies have found that using MSCs for therapy in people is generally safe, with only minor side effects like temporary fever or discomfort at the injection site. However, there are still challenges in using MSCs effectively for treatment. In order to improve their performance, scientists are exploring different approaches.
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Using MSC-Derived Vesicles: Instead of using whole MSCs, researchers are looking at tiny particles called extracellular vesicles (EVs) that MSCs release. These EVs seem to have similar or even better healing abilities for diseases like rheumatoid arthritis (RA) and lupus. They can influence the immune system and help reduce inflammation. Using EVs might be safer than using whole MSCs.
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Biomaterial Strategies: Scientists are also trying to make MSCs work better by using special materials like hydrogels, microspheres, and scaffolds. These materials can help MSCs stay in the right place and release healing substances for a longer time.
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Preconditioning and Genetic Modification: MSCs can be treated before use to make them more effective. This process, called preconditioning, involves exposing MSCs to certain substances or conditions. It can enhance their ability to heal and regulate the immune system. Another approach is genetic modification, where scientists change the genes of MSCs to make them produce helpful substances. These modified MSCs can be more powerful in treating diseases.
Conclusion
MSC-based therapies show promise in treating systemic rheumatic diseases, but they face challenges such as variability, immune responses, stability, and cell migration. To overcome these obstacles and enhance effectiveness, researchers are exploring innovative approaches like genetically modified cells and extracellular vesicles (EVs). Ongoing research and clinical trials aim to assess the safety and efficacy of MSC therapy for these diseases. To ensure safety, donors are screened for infections and genetic issues, and the quality of stem cells is checked. Patients undergo medical assessments to determine suitability, and close monitoring during and after treatment helps detect any adverse effects. Overall, MSC-based therapies offer a potentially safer and more effective alternative to conventional treatments for systemic rheumatic diseases, with ongoing advancements in technology and understanding.
