Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can damage many different parts of the body, including the kidneys, lungs, brain, and blood system. Because it can attack so many organs, it often leads to serious illness and even death.
For many years, doctors have used medications like corticosteroids, cyclophosphamide (CTX), and mycophenolate mofetil (MMF) to control the disease. These treatments have helped patients live longer and have reduced the chances of severe organ failure. However, even with these medications, controlling SLE can still be very difficult for some patients.
Researchers have also developed newer drugs that target specific parts of the immune system, such as rituximab, belimumab, and tocilizumab, among others. While these drugs have improved outcomes for many people, they can sometimes cause serious side effects or lead to the disease coming back once the medication is stopped. Because of these challenges, scientists have been searching for new ways to treat SLE, and one promising option is stem cell therapy.
As part of this review, Yuan et al. explore how stem cells are being used to treat lupus, including the different types of stem cells, the challenges involved, and what the future of treatment may hold.
Hematopoietic Stem Cells and Their Role in Lupus Treatment
Hematopoietic stem cells (HSCs) are the type of stem cells that create all other blood cells. First discovered in 1961, HSCs have become important in treating both blood cancers and autoimmune diseases. In 1997, doctors began using HSC transplants (HSCT) to treat patients with both blood cancers and autoimmune diseases. The results demonstrated that not only did the cancers improve, but the autoimmune symptoms also got better.
Since then, many studies around the world have tested HSCT in people with SLE, and the results have been very encouraging – with patients even showing signs of what researchers call a “fundamental cure,” meaning their disease improved dramatically over the long term.
How Lupus Affects Stem Cells
SLE itself can harm the body’s natural stem cells. Research has shown that people with lupus have lower levels of circulating HSCs and endothelial progenitor cells (which help repair blood vessels). This loss of stem cells may be caused by an increase in programmed cell death, known as apoptosis. As a result, lupus patients may have a harder time repairing blood vessels, leading to problems like atherosclerosis (hardening of the arteries).
Other studies have found that certain changes in the immune system can make stem cells more likely to die off. For example, increased activity in a pathway called mTOR has been linked to poor blood cell production in mice with autoimmune diseases. However, research has also shown the opposite, with lupus conditions causing an increase in stem cells that behave abnormally.
Because of these differences, the authors indicate the need for further research to fully understand how lupus affects stem cells.
Comparing Hematopoietic and Mesenchymal Stem Cells
Because of the challenges with hematopoietic stem cells, researchers have also explored using mesenchymal stem cells (MSCs). MSCs come from bone marrow, fat tissue, or umbilical cord blood, and they have powerful anti-inflammatory and immune-regulating effects.
Clinical studies have shown that about 60% of patients responded well to the treatment, and there were very few serious side effects. This finding opened the door to a whole new field of lupus treatment research.
One significant difference between HSCT and MSC therapy is that MSCs do not require the intense and risky immune system wipe-out that HSCT does. Instead, MSCs can be infused into the body and work to rebalance the immune system naturally. Because of this, MSC therapy is generally safer, has fewer complications, and is more affordable than HSCT.
Another reason MSCs are so promising is that bone marrow MSCs from lupus patients often show structural and functional abnormalities, which means that transplanting healthy MSCs from a donor could help correct some of the immune system issues at the root of the disease.
Animal studies have strongly supported the effectiveness of MSCs in treating lupus, and early clinical trials in humans have shown encouraging results. Phase I and II studies suggest that MSC therapy is both safe and effective for SLE patients, but further larger clinical trials are needed to confirm these findings and to better understand exactly how MSCs help heal the immune system.
The Future of Stem Cell Therapy for Lupus
Stem cell therapy offers exciting new possibilities for patients with SLE who have not had success with traditional treatments. Hematopoietic stem cell transplants have been shown to help many patients, sometimes even achieving long-term remission. However, because of the high risks and costs involved, HSCT is likely to remain a treatment reserved for the most severe and treatment-resistant cases.
Mesenchymal stem cell therapy, on the other hand, appears to offer a safer, more accessible option that could benefit a much larger number of patients. With fewer side effects, lower relapse rates, and easier treatment protocols, MSCs are quickly becoming a major focus of research into better lupus treatments.
At the same time, the authors continue to study exactly how stem cells work to regulate the immune system. They are also working on ways to improve the safety and effectiveness of both HSCT and MSC treatments. According to Yuan et al, goals for the future include finding better ways to prevent infections, lowering relapse rates, and understanding the long-term effects of stem cell therapy. Researchers are also exploring how to personalize stem cell therapies based on each patient’s unique immune system and genetic background, which could lead to even better outcomes.
Yuan et al. conclude that while traditional lupus treatments have made great strides over the past few decades, there is still a significant need for new and better therapies, especially for patients whose disease does not respond to standard medications.
Stem cell therapy, particularly with mesenchymal stem cells, represents a promising new frontier in the fight against lupus. Ongoing research and clinical trials will help clarify how best to use stem cells to treat SLE safely and effectively, offering new hope for people living with this challenging disease.
Source: Yuan X, Sun L. Stem Cell Therapy in Lupus. Rheumatol Immunol Res. 2022 Jul 6;3(2):61-68. doi: 10.2478/rir-2022-0011. PMID: 36465325; PMCID: PMC9524813.
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