by admin | Oct 11, 2019 | Mesenchymal Stem Cells, Exosomes, Osteoarthritis
The field of Regenerative Medicine has shown great promise for helping those with a variety of chronic diseases, including arthritis. Indeed, data on the potential value of using stem cells to address issues relating to arthritis have been growing. While specific stem cells like mesenchymal stem cells have demonstrated therapeutic effects in models of arthritis and other inflammatory diseases, the specific ways in which these cells confer their benefits are not yet well understood. Given that these stem cells contain different types of elements, it is important that research establishes which of these elements is critical to the therapeutic properties of stem cells.
A recent study, published in Theranostics, looked specifically at the different effects that small exosomes and larger microparticles from within mesenchymal stem cells have on the inflammatory processes that occur in arthritis. To conduct their experiment, scientists isolated the exosomes and microparticles from mesenchymal stem cells using an ultracentrifugation technique and then exposed the exosomes and the microparticles to cells of the immune system – specifically, T and B lymphocytes, which are implicated in arthritis.
What the researchers found was that, in their models of arthritis, both the exosomes and the microparticles suppressed the T lymphocyte proliferation that is indicative of inflammation. However, unlike microparticles and even parental mesenchymal stem cells, the exosomes were also able to induce other anti-inflammatory effects. The result of exosome activity was, therefore, more efficient blunting of inflammation.
These results point to the potential of not just stem cells, but specifically the exosomes of these cells, in therapeutically addressing inflammatory arthritis. While more research is needed to understand how these exosomes could actually impact arthritis patients, these data provide hope that stem cells and even just elements of stem cells will help these patients by improving their ability to combat problematic inflammation.
Reference: Cosenza, S. et al. (2018). Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis. Theranostics, 8(5), 1399-1410.
by admin | Sep 21, 2019 | Health Awareness, Osteoarthritis, Pain Management
Joint pain and inflammation are common characteristics of arthritis. While many individuals use prescription medications to manage their discomfort, other lifestyle modifications such as dietary changes, regular exercise, and herbal supplements may help as well. In particular, certain herbs appear to minimize joint pain more so than others. Although clinical studies on the effectiveness of using the following herbal remedies for joint pain have been limited, the research that has been performed is promising. The following 5 plants that help control joint pain.
Turmeric
The yellow spice commonly used in Indian food has an orange pulp within its stem, which is where the plant compound curcumin is housed. This powerful agent has demonstrated an ability to reduce chronic inflammation caused by rheumatoid arthritis. Yet, because the body can only absorb so much curcumin, its benefits may be limited.
Eucalyptus
Oils can be distilled from the eucalyptus plant and used for anti-inflammatory properties. They are also believed to hold antiviral and antibacterial benefits. The tannins and flavonoids within the leaves are antioxidants, which could help to minimize the joint inflammation and pain experienced in arthritis. Eucalyptus oil can be diffused or added to a warm bath, though many individuals have an allergy to the plant.
Frankincense
Hailing from the bark of the Boswellia tree, frankincense has an aromatic quality, making it a popular ingredient in perfumes and incense. It can be inhaled, applied directly to the skin, or taken as a supplement. The herb is also believed to prevent leukotrienes, the compounds responsible for inflammation. It has even been shown to be as effective as NSAIDs for addressing joint pain in conditions like osteoarthritis and rheumatoid arthritis, but with fewer side effects.
Aloe Vera
Aloe is often the plant that many people reach for to treat burns, as it has both anti-inflammatory and antimicrobial properties. Yet, its anti-inflammatory benefits can be realized by people with arthritis, too. The plant inhibits the production of inflammatory enzymes, which may help to control joint pain.
Borage Oil
The starflower plant contains seeds which are rich in an omega-6 fatty acid known as gamma-linolenic acid (GLA). When metabolized, GLA converts into a signaling molecule which helps regulate inflammatory responses within the body. Certain oils with GLA have been shown to alleviate pain in individuals with rheumatoid arthritis, but borage seed oil is believed to be the most effective because it protects cells from oxidative stress which could be caused by high concentrations of GLA.
While herbal remedies, unfortunately, cannot cure arthritis, they may make a noticeable difference in pain levels, swelling, and stiffness. For individuals who are seeking an alternative to NSAIDs or other drugs, trying plant-based alternatives may be a worthwhile therapeutic option to consider.
by admin | Jul 8, 2019 | Exosomes, Osteoarthritis, Stem Cell Research, Stem Cell Therapy
Osteoarthritis is the most common form of arthritis. About one in 10 people will develop osteoarthritis at some point in their lifetimes. As the condition progresses, synovial membranes and cartilage break down. Osteoarthritis causes people to experience joint pain, joint stiffness, and restricted movement. Knees, hips, and hands are common sites for arthritis, though people can experience the condition in virtually every joint in the body including joints and spine. Mild osteoarthritis may be nothing more than an annoyance, but moderate and severe osteoarthritis can diminish a person’s quality of life and cause substantial suffering and disability.
Despite the commonness of osteoarthritis, there are very few effective treatment options. People may take pain medications to help cope with discomfort; however, taking these medications every day can lead to unwanted side effects. Physical therapy, braces, walking aids, and exercise may have some effect, but their benefit is unpredictable, i.e., these approaches work for some people and not others. The only definitive treatment for osteoarthritis is to replace the joint with an artificial one; however, orthopedic surgery is expensive, associated with a long recovery, and is usually only an option after patients have suffered pain and disability for a long period of time.
Ideally, osteoarthritis treatment would be focused on restoring the structure of the damaged joint itself. For a time, physicians were hopeful that glucosamine and chondroitin could do this. These two substances are diminished in osteoarthritis, so the concept was to replace them and hopefully rebuild damaged joints. While initial clinical studies seemed to suggest glucosamine and chondroitin were helpful, larger, high-quality clinical trials failed to show any benefit. Nevertheless, the goal of repairing joints damaged by osteoarthritis is still a top goal. Now, however, scientists have turned to stem cells instead of small molecules.
Stem cell researchers are particularly interested in the small sacs released by stem cells called exosomes. Exosomes contain proteins, RNA, cytokines, and other substances that are important for tissue regeneration. Exosomes are apparently responsible for most of the clinical benefit of stem cells in the first place. Moreover, it is much more convenient for doctors to use exosomes as treatment rather than stem cells themselves.
To this end, researchers have been studying the effects of stem cell exosomes. One research group recently published a report studying the effects of exosomes that were collected from synovial membrane stem cells and compared them to exosomes taken from induced pluripotent stem cells. Synovial membrane stem cells are an obvious choice for treating osteoarthritis since synovial membranes are one of the substances that break down in the disease. However, synovial membrane stem cells are difficult to obtain. It is far more practical to use induced pluripotent stem cells since there is a virtually limitless supply of them.
The researchers compared exosomes taken from these two types of stem cells in mice with experimental osteoarthritis. Not only did the scientists show that exosomes taken from pluripotent stem cells were highly effective in treating osteoarthritis, these exosomes were even more effective in treating osteoarthritis then exosomes taken from synovial membrane stem cells. Exosomes from pluripotent stem cells not only repaired synovial membranes but they also helped replace cartilage by stimulating chondrocytes (cartilage cells).
Of course, this work will need to be confirmed in humans with osteoarthritis; however, the results of this animal research are very encouraging. In short, this research suggests that exosomes taken from induced pluripotent mesenchymal stem cells may be a convenient and effective way to treat osteoarthritis in the future.
Reference: Zhu, Y. et al. (2017). Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Research and Therapy. 2017 8:64.
by admin | Mar 4, 2019 | Mesenchymal Stem Cells, Osteoarthritis
Osteoarthritis is the most common form of arthritis. In fact, when people casually use the term “arthritis” or think of the arthritis of old-age, they are usually talking about osteoarthritis. People with arthritis experience many symptoms in and around the affected joints including pain and swelling. The affected joints may become unstable or “give out.” At the same time, people who suffer from osteoarthritis may not be able to move their joints fully or smoothly. Commonly people feel that their joints are “stiff.”
Early in osteoarthritis, the pain may just occur occasionally. Perhaps, the person feels sharp pain when moving a certain way. In later stages of osteoarthritis, the affected joints constantly ache, and moving the joint becomes intensely painful.
Nonsteroidal anti-inflammatory drugs or NSAIDs can help in some cases, but they become less effective as osteoarthritis becomes more severe. Often people with osteoarthritis must receive injections of anesthetics and steroids into the joints itself. Ultimately, patients often need orthopedic surgery to grind away diseased joint tissue or even replace the joint with the artificial one.
Researchers are searching for ways to reverse osteoarthritis instead of just treating the symptoms. Fortunately, stem cells may offer hope. Doctors have long known that in people with osteoarthritis, the cartilage becomes thin and breaks down. Joint cartilage lubricates the joint, acts as a shock absorber, and helps the joint move smoothly. When cartilage breaks down, the joint becomes stiff, painful, and irritated. As recent research suggests, mesenchymal stem cells may rebuild and restore joint cartilage.
Two scientists, Kristjánsson and Honsawek, recently reviewed the state of the research in this field. They identified eight clinical studies that tested mesenchymal stem cells on patients with varying degrees of osteoarthritis. The clinical trials demonstrated several intriguing findings. Most notably, mesenchymal stem cells were able to promote cartilage regeneration, reduce pain, and improve joint function. The scientists also found that the more stem cells that were injected, the better the outcome. In addition, the beneficial effect of stem cells occurred whether the cells were taken from the patient (autologous stem cells) or from young, healthy donors (allogenic stem cells).
Importantly, patients with mild to moderate osteoarthritis enjoy the greatest apparent benefit from stem cell injections. This suggests that doctors and patients should consider stem cell treatment earlier in the course of osteoarthritis before joints become too damaged and likely require surgery.
Mesenchymal stem cell injection for osteoarthritis has now been tested in at least eight clinical studies including randomized clinical trials, which are the gold standard studies for evaluating treatments in medicine. Research is ongoing and still needed but these results are strongly encouraging. They may offer, for the first time, a way for patients to reverse the changes of osteoarthritis rather than simply treating the symptoms of the disease.
Reference: Kristjánsson et al. (2017). Mesenchymal stem cells for cartilage regeneration in osteoarthritis. World Journal of Orthopedics. 2017 Sep 18; 8(9): 674–680.
by admin | Mar 1, 2019 | Mesenchymal Stem Cells, Osteoarthritis, Stem Cell Therapy, Studies
Cartilage plays several important roles in the way joints move and function. Joint cartilage provides lubrication, acts as a shock absorber, and helps the joint move smoothly. Joint cartilage is comprised of two substances chondrocytes (i.e. cartilage cells) and extracellular matrix (proteins such as hyaluronic acid, collagen, fibronectin, etc.).
Many conditions can lead to joint cartilage defects. In young people, the most common cause of the joint cartilage defect is an injury. For instance, a football player suffers a hard contact that injures the joint. Another example is a gymnast who repeatedly places substantial impact forces on the knee and other joints of the lower body, resulting in damage. In older people, the most common cause of joint cartilage defects is Osteoarthritis. Over time, the joint cartilage breaks down in the cartilage loses its ability to lubricate, absorb shock, and support the smooth movement of the joint. This leads to stiffness, pain, and “trick” joints, among other symptoms.
Orthopedic surgeons, rheumatologists, and other physicians have attempted to treat these conditions by injecting the damaged joint with one of the two main components of joint cartilage: extracellular matrix. Physicians inject hyaluronic acid (and sometimes related extracellular matrix proteins) to help replace and restore damaged joints. This approach can be helpful for some patients, but it is certainly not a cure.
Only recently, have researchers attempted to replace the other component of joint cartilage: chondrocytes. Specifically, researchers have focused their efforts on mesenchymal stem cells that have the ability to differentiate and become cartilage cells. Li and colleagues injected combinations of bone marrow-derived mesenchymal stem cells and hyaluronic acid into animals with experimental cartilage defects. They showed that hyaluronic acid injections alone modestly repaired the cartilage damage. However, when stem cells plus hyaluronic acid was injected, the joints were almost completely repaired. In other words, stem cells plus hyaluronic acid resulted in much greater improvement in joint cartilage damage than hyaluronic acid alone.
The authors of the study concluded that “bone marrow stem cells plus hyaluronic acid could be a better way to repair cartilage defects.” While additional work is needed, these results are extremely exciting for people who suffer from joint cartilage defects such as osteoarthritis. In the future, people who are candidates for hyaluronic acid injection treatments may instead receive a combination of hyaluronic acid plus stem cells and may enjoy an even greater benefit than hyaluronic acid treatment alone.
Reference: Li et al. (2018). Mesenchymal Stem Cells in Combination with Hyaluronic Acid for Articular Cartilage Defects. Scientific Reports. 2018; 8: 9900.
by admin | Dec 29, 2018 | Mesenchymal Stem Cells, Osteoarthritis, Stem Cell Therapy
Most large joints of the body contain cartilage, a substance that is softer and more flexible than bone. Because of its softness and flexibility, cartilage is well-suited to protect the bones as they move across one another. Unfortunately, this softness and flexibility also makes cartilage prone to injury and erosion. In patients with osteoarthritis, forexample, cartilage breaks down to the point that bone rubs against bone,causing pain and disability. Certain injuries can damage the cartilage (i.e.osteochondral lesion), which can essentially have the same effect.
Once the cartilage of joints has become damaged, there is
little that can be done to fix it. Patients may receive steroid injections into
the joint to reduce inflammation, and may rely on pain medications to relieve
the pain and swelling. Short of joint replacement therapy, no treatments can
reverse cartilage damage once it has occurred.
Fortunately, mesenchymal stem cells may soon be able to reverse cartilage defects that arise from osteochondral lesions and osteoarthritis. Wakitani and colleagues took samples of patients’ bone marrow, which contains mesenchymal stem cells. They then used various laboratory techniques to increase the number of stem cells in the sample. Four weekslater, the researchers then reinjected the concentrated stem cells back intothe same patient using their own source of stem cells. The Wakitani groupshowed that stem cell transplantation improved the patient’s clinical symptoms bysix months, a benefit that continued for two years on average. Samples takenfrom the patients 12 months later showed that the damaged cartilage had beenrepaired. In other work, Centeno and co-authors showed that bone marrow-derived mesenchymal stemcells could increase the volume of cartilage, reduce pain, and increase rangeof motion 24 weeks after stem cell transplantation.
Research continues to determine which stem cells are most useful, how many stem cells should be injected, how many injections need to be administered, and how should those stem cells be prepared before they are injected? Nonetheless, certain groups are making great strides in this area. In fact, the recent discovery of human skeletal stem cells promises to accelerate stem cell research into treating disorders of bone and cartilage.
Reference
Schmitt et al. (2012). Application of Stem Cells in Orthopedics. Stem Cells International. 2012: 394962
St. Petersburg, Florida
