Over the past decade, scientists have learned that the molecules that mesenchymal stem cells release are every bit as important to regenerative medicine as the stem cells themselves. Stem cells release exosomes, which are tiny packets that contain countless molecules of microRNA, cytokines, and growth factors. These molecules are mainly what allows stem cells to help the body regrow and repair.
Dr. Vizoso and colleagues published a review article that describes the many benefits of the secretome, that is, stem cell exosomes and the substances they produce. They not only explain why exosomes are helpful in regenerative medicine but why stem cell exosomes bring a powerful enhancement to stem cells themselves.
Compared to exosomes, whole stem cells are rather big—one can safely inject far more exosomes than stem cells in each treatment. And, really, it seems that the stem cell exosomes are what is supplying most of the benefits.
Stem cells can be made to produce millions of exosomes. These stem cell exosomes can then be collected, stored, shipped, and infused with much less cost and aggravation than stem cells themselves. Exosomes have small molecules on their surfaces that allow them to seek out and find areas in the body where they are needed. Stem cells often need to be injected near the site of injury. Exosomes may work if simply infused into a vein.
Dr. Vizoso and coauthors make a persuasively strong argument about the potential benefits of infusing stem cell exosomes instead of stem cells themselves. They also point out the potential limitations of the process, given the current technology. For example, stem cells would need to be made “immortal” so that they can keep producing large amounts of the same sorts of exosomes over time. Fortunately, the techniques of cell immortalization have been around for at least 30 years. Thus, most of the barriers to widespread, large scale exosome use are things scientists already know how to overcome.
While there may still be benefits for direct stem cell infusions, the future of research is moving forward with stem cells and exosomes.
Reference: Vizoso, F., et al. (2017). Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine. International Journal of Molecular Sciences. 2017, 18(9), 1852.
Rheumatoid arthritis (RA) is a chronic inflammatory condition that can affect the joints, as well as several body systems. As an autoimmune disease, RA is characterized by the body’s immune system mistakenly attacking its own healthy tissue. While other forms of arthritis, such as osteoarthritis, are caused by general wear and tear, RA targets the joint lining, resulting in swelling that will eventually erode the joints and bones.
In some cases, the inflammation can cause widespread damage throughout bodily systems such as the eyes, skin, lungs, heart, and blood vessels. Although there have been treatments available to control the symptoms of RA, in some severe cases, physical disabilities may still occur.
Can Stem Cell Therapy Help Treat Rheumatoid Arthritis?
Typically, RA is treated with immune suppressive medications such as steroids. While they may offer temporary relief, long-term use isn’t advised, as it can suppress the body’s immune response. Thus, such medications leave patients more vulnerable to infections and other illnesses. Disease-modifying anti-rheumatic drugs (DMARDs) may be prescribed as well, or biologics if needed. Nonetheless, these medications fail to address joint damage which has already occurred. Moreover, many patients fail to see significant results.
Recently, stem cell therapy has emerged as a studied and researched option to target inflamed tissue and trigger the development and anti-inflammatory agents. Mesenchymal stem cells (MSCs), in particular, have been shown to produce T regulatory cells, which help to safeguard against the self-attacking immune response seen in RA. One study on MSCs for RA demonstrated a significant decrease in pro-inflammatory agents, absent of the long-term side effects caused by traditional RA therapies.
Which Type of Stem Cells Are Used to Treat Rheumatoid Arthritis?
MSCs are a commonly used stem cell therapy option for managing symptoms of Rheumatoid Arthritis. These cells are derived from either adipose (fat) tissue from the patient or the umbilical cord (Wharton’s Jelly) following healthy births. The mothers undergo rigorous screening to ensure the safety of the cells. Because umbilical cord-derived stem cells are some of the youngest, they have longer cell lives than those derived from adults.
What Are the Benefits of Mesenchymal Stem Cells?
Since they are do not come from the blood, MSCs are considered safe and do not require phenotypic or Hyman Leukocyte Antigen (HLA) matching. Cell rejection is therefore not a concern. Mesenchymal stem cells exert a number of beneficial effects on the cells of the immune system. Mesenchymal stem cells can help fine-tune the immune system by inducing the action of regulatory T-cells potentially shifting the balance from harmful to helpful immune system function.
The benefits of MSCs leave researchers optimistic about the future of stem cells as an option for those with autoimmune conditions such as Rheumatoid Arthritis. The therapy is a worthwhile option to explore for patients seeking potential improvements for their day to day quality of life. Contact a Care Coordinator today for a free assessment!
Scientists have long realized that multiple sclerosis is an inflammatory disease, and that the immune system, in a manner, attacks the brain and spinal cord. These inflammatory lesions cause patients to have severe neurological symptoms. Therefore, treatments for multiple sclerosis have focused on controlling the immune system.
There are current treatments of care for MS patients to manage their symptoms. They can help minimize the severity of the disease, but they may cause serious side effects. Consequently, researchers are constantly looker for newer, safer, less expensive alternatives.
While the precise cause of MS is still unknown, multiple sclerosis lesions contain high levels of an immune cell, specifically CD4+ T cells. These T cells become active in the central nervous system and interfere with the function of other T cells (regulatory T cells). Simply put, whatever causes MS creates abnormal regulatory T cells; healthy regulatory T cells are important for maintaining a balance between helpful and harmful immune system functions.
The scientists collected mesenchymal stem cells from umbilical cord tissue (the tissue that is usually thrown away as medical waste after live birth). They also collected peripheral blood mononuclear cells (i.e. T cells, B cells, natural killer cells, and monocytes) from patients with MS and healthy volunteers. Stem cells and peripheral blood mononuclear cells were combined in the lab for 3 days. After incubation, samples with stem cells had a higher proportion of regulatory T cells, and those regulatory T cells had greatly improved their function. In fact, stem cell treatment made the defective regulatory T cells function much like regulatory T cells from healthy volunteers.
More work must be done to take this technology from the lab and into the clinic, but the proof of concept is remarkable. Stem cell treatment has been shown to be safe in scores of clinical trials. Thus, if umbilical cord-derived mesenchymal stem cells can improve regulatory T cell function in patients with MS, the impact could be beneficial to help improve multiple sclerosis symptoms.
Reference: Yang, H., et al. (2016). Umbilical cord-derived mesenchymal stem cells reversed the suppressive deficiency of T regulatory cells from peripheral blood of patients with multiple sclerosis in a co-culture – a preliminary study. Oncotarget 2016; 7:72537-72545.
The most common form of multiple sclerosis is a relapsing-remitting MS. In relapsing-remitting multiple sclerosis, patients have relatively quiet, healthy times interrupted by disease flares. MS flares can cause many different neurological symptoms. The disease can interfere with any number of bodily processes, from walking to seeing, to urinating.
For many years, the only treatments available for relapsing-remitting MS were steroids or other powerful medications that had troubling side effects. Recently, disease-modifying drugs have become available that extend the times in between flares. Steroids are still used to treat disease flares, but disease-modifying drugs seem to make those flares occur less often.
One way that scientists judge the value of disease-modifying therapy for relapsing-remitting MS is to see how long it can prevent relapse. For example, researchers divide a group of patients into two groups, give each group a different treatment, and track to see the time until a relapse occurs.
Researchers took this same scientific approach to compare disease-modifying therapy to nonmyeloablative hematopoietic stem cell transplantation which is the infusion of stem cells without destroying the patient’s existing bone marrow and stem cells with chemotherapy. The results were published in the prestigious Journal of the American Medical Association (JAMA).
The scientists from hospitals and institutions around the world followed about 100 women with relapsing-remitting multiple sclerosis. Half received disease-modifying therapy, which is the current standard of care, while the other half received stem cell therapy.
During the first year of the study, the symptoms were more severe in patients who received disease-modifying therapy. This was expected since patients with this form of MS tend to get worse over time. Impressively, the group who received stem cell treatment had less severe symptoms than when they started a year earlier.
Three patients who received stem cell therapy experienced disease progression; however, a staggering 34 patients in the disease-modifying group had disease progression. In other words, far fewer RRMS patients in the stem cell therapy group had disease progression than those receiving standard disease-modifying treatments.
The authors of this groundbreaking study mention that “further research is needed to replicate these findings,” presumably in a double-blind trial. Nevertheless, this is not a small study (~100 patients) and patients were followed for a very long time (5 years). As such, the results provide strong, preliminary evidence that stem cell therapy was more effective than disease-modifying therapy for patients with
Reference: Burt, R., et al. (2019). Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis. JAMA. 2019;321(2):165-174.
Lupus is a long-term illness which can lead to inflammation and pain in any part of the body. As an autoimmune condition, lupus is characterized by an immune response in which the body mistakenly attacks healthy tissue. Oftentimes, the condition affects the skin and joints. In serious cases, it can also affect the internal organs, such as the kidneys and heart. Common symptoms include rash, fatigue, and swollen lymph nodes.
There is currently no cure for lupus, though medications such as anti-inflammatory drugs and immune-suppressants are used to control symptoms. In severe cases, cytotoxic drugs may be prescribed. These medications target and destroy cells that grow at a rapid rate. In the case of autoimmune conditions, the hyperactive immune system produces autoantibodies too rapidly, and the medications may help to control this response.
Unfortunately, drugs such as cytotoxic medicines have a number of unfavorable side effects, including toxic effects on the blood and immune systems. Patients become more vulnerable to infections such as pneumonia, and hair loss is a common side effect.
Frustratingly, lupus can be a painful and debilitating illness, and patients are left with few treatment options. Moreover, not all patients respond to medications as desired.
Stem Cell Therapy for Lupus
Any successful therapy for lupus should help to control the flare of symptoms and balance the body’s immune response. While achieving this harmony has proven difficult with traditional therapies, recent research suggests stem cell treatment could hold the potential in helping to manage the symptoms of this autoimmune condition.
In particular, the intravenous administration of a patient’s own stem cells could help to regulate the body’s immune response, restoring function in the organs affected by the illness while simultaneously minimizing or eliminating the need for certain medications.
Stem cells can give rise to virtually any cell tissue within the body. They also have the ability to repair damaged tissue because they have the ability to multiply. Within recent years, studies involving stem cell therapy have been performed, offering immense promise to patients with autoimmune conditions seeking alternative treatment options. Contact a Care Coordinator today for a free assessment!
Odds are, you or someone you know has osteoarthritis—it is that common. Osteoarthritis is a chronic inflammation and destruction of one or more joints. Osteoarthritis is the kind of arthritis most people think of when they think of “arthritis.” The disease usually causes joint pain, stiffness, and limited joint motion. Common sites of osteoarthritis are the hands, knees, feet, spine, and hips.
Unlike rheumatoid arthritis, there are few good treatments for osteoarthritis. Most people with advanced disease must take analgesics (painkillers) each day to dull the pain. Unfortunately, each painkiller comes with its own problems. Aspirin increases the risk of bleeding. NSAIDs like ibuprofen wreak havoc on the gastrointestinal system and affect the kidneys. Chronic acetaminophen can be harmful to the liver. Opioids come with the risk of dependence and addiction. The only definitive treatment for osteoarthritis is surgery, which is expensive and usually requires a long recovery period.
Mesenchymal stem cells, also known as stromal cells, have shown remarkable promise in the treatment of osteoarthritis. For example, mesenchymal stem cells taken from bone marrow or fat tissue (adipose) that are then injected into joints can protect the joint from degeneration and slow the progression of osteoarthritis. However, there are some limitations with stem cell treatment. One issue is that only so many cells can be injected in a space at once. For these reasons, scientists have pivoted some of their focus from stem cells to the tiny packets of information stem cells release called exosomes.
Exosomes contain millions of beneficial molecules including small proteins, cytokines, RNA, microRNA, and DNA. One stem cell can release thousands of exosomes. Since the exosomes are so small, many more exosomes can be collected and injected than stem cells themselves.
Researchers recently showed that exosomes collected from mesenchymal stem cells were able to provide the same benefits against osteoarthritis in mice as bone marrow stem cells did themselves. Stem cells slowed down the clinical signs of arthritis in mice just as whole stem cells did. Exosomes also protected cartilage and other joint structures from destruction.
This research demonstrates the developing science to use exosomes to treat osteoarthritis instead of the stem cells themselves. This gives doctors (and patients) considerably more flexibility in how they approach treatment. Exosomes tend to find their way to sites of disease, meaning they may be able to be injected into a vein instead of injected in the diseased joint. In addition, patients may be able to receive a higher “dose” of exosomes when simply purified exosomes are injected. This exciting research will need to be extended to humans, but clinical trials are in the planning phase.
Reference: Cosenza, S., Ruiz, M., Toupet, K. et al. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci Rep 7, 16214 (2017).
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