Mesenchymal Stem Cells Injection Improves Hip Osteoarthritis

Mesenchymal Stem Cells Injection Improves Hip Osteoarthritis

Osteoarthritis of the hip is a painful condition that can interfere with leg movement and diminish the quality of life. In some, the symptoms are mild, but in others, osteoarthritis can be severe and can even lead to joint failure. Pain is often intermittent in early stages, but in later stages, the pain can be constant with periods of sharp, intense pain. The hip joint becomes stiff and unstable, making it difficult to move around and greatly increasing the risk of falls.

Unfortunately, there are few effective treatments for osteoarthritis of the hip. Management includes pain control with non-steroidal anti-inflammatory drugs and physical therapy. Steroid injections into the hip are not as effective as they are for knee osteoarthritis, so many doctors hesitate to perform them. Joint supplements such as glucosamine and chondroitin are unlikely to be very effective—clinical trials have not provided evidence that they actually work. The definitive treatment for hip osteoarthritis is hip replacement surgery, which is expensive and associated with a long period of recovery.

The main problem in osteoarthritis is that the joint breaks down over time from wear and tear (i.e. microtraumas). At the same time, the joint has a very limited capacity to heal itself. In other words, once the joint breaks down, it pretty much stays that way. Since life is a series of joint microtraumas, the hip gets progressively worse. Indeed, one in four people will have painful osteoarthritis of the hip by age 85, and hundreds of thousands will have it earlier in life.

Scientists have long wanted to find ways to help the body regenerate the joint substances, particularly joint cartilage. Unfortunately, the joint does not receive good blood supply and no known drug or supplement can actually rebuild joint cartilage. That is the main reason researchers are aggressively testing stem cells as a treatment for hip osteoarthritis.

Mesenchymal stem cells have the potential to become many different types of cells, including chondrocytes (cartilage cells). Mesenchymal stem cells sense the environment they are in and then become the cell consistent with that environment. So, the theory goes, injecting mesenchymal stem cells into the hip joint can prompt them to become hip joint cells (chondrocytes).

Researchers tested this hypothesis in a clinical study. They injected mesenchymal stem cells taken from fat tissue (i.e. adipose) and injected them into the hip joints of people with difficult-to-treat hip osteoarthritis. They compared the patients’ Harris Hip scores (HHS) before and 6 months after treatment. HHS is a reliable way to assess the severity of osteoarthritis symptoms. An HHS score of less than 70 is “poor” and a score of 80 to 90 is “good.” Before stem cell treatment, patients had an average HHS score of 67.2±3.4 and 84.6±6.3 afterward. Scores also improved in other tests including WOMAC and Visual Analogue Scale. In other words, mesenchymal stem cell treatment reduced pain and improved joint function in these patients compared to levels prior to treatment.

The authors of the clinical study state that “preliminary results are positive and promising.” Further research and studies will help to learn more about this regenerative medicine potential.

Reference: Dall’Oca, C. et al. (2019). Mesenchymal Stem Cells injection in hip osteoarthritis: preliminary results. ACTA Biomedica. 2019, 90(Suppl 1): 75-80.

Mesenchymal Stem Cells Can Modulate the Immune System

Mesenchymal Stem Cells Can Modulate the Immune System

The human immune system can be one of our biggest assets or one of our greatest foes. The immune system protects us against foreign invaders like viruses and bacteria. It is essential for helping us maintain immunity over a lifetime, whether from immunizations or previous infections. We could not live without our immune systems.

On the other hand, the human immune system is the cause of numerous diseases. Autoimmune diseases like multiple sclerosis, ulcerative colitis, systemic lupus erythematosus, and Crohn’s disease are caused by an immune system that mistakenly attacks our own tissue. Organ and bone marrow transplants fail because the body’s immune system rejects the transplant. When the immune system is functioning normally, it is life-sustaining; however, when the immune system falters, it can cause serious disease, suffering, and even death.

Compared to other diseases, the treatments for autoimmune diseases and other diseases that involve the immune system are limited. Doctors can prescribe steroids to knock down the immune response. These powerful drugs can control disease flareups, but they aren’t a cure. Moreover, steroids cause terrible side effects when taken long-term.

While there have been some recent developments in the treatment of certain autoimmune diseases (e.g. disease-modifying drugs for inflammatory bowel disease), medications are still limited. That is why scientists are actively studying the immune-modulating power of mesenchymal stem cells.

Mesenchymal stem cells exert a number of beneficial effects on the cells of the immune system. Mesenchymal stem cells can suppress T-cells, B-cells, dendritic cells, and natural killer cells (cells that participate in autoimmune diseases). Likewise, mesenchymal stem cells induce and affect the action of regulatory T-cells. This can help fine-tune the immune system, potentially shifting the balance from harmful to helpful immune system function.

Mesenchymal stem cells have been shown to be effective in various Phase I and Phase II clinical trials to treat multiple sclerosis, Crohn’s disease, lupus, ulcerative colitis, and even diabetes. While the clinical trials are often small—15-40 patients—the effects are impressive. Furthermore, treatment with mesenchymal stem cells is consistently safe; in study after study, the risk of serious adverse events is vanishingly small.

As with most fields of medicine, these clinical trials will need to be replicated in larger, Phase III trials. That being said, some large trials have already been conducted with favorable results. Perhaps the best example of a large trial testing the effect of mesenchymal stem cells on immune system function is in the field of transplantation medicine. The prestigious Journal of the American Medical Association (JAMA) published a clinical trial of 159 patients undergoing kidney transplants. Stem cell treatment reduced the incidence of kidney rejection, decreased the risk of opportunistic infection, and was associated with better kidney function 1 year after treatment.

The results from dozens of clinical trials suggest mesenchymal stem cells are powerful modulators of immune cell function and have the potential to one day be tools to treat diseases caused by the immune system. We anxiously await further results from large, Phase III trials.

Reference: Gao, F., et al. (2016). Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death & Disease. 2016, Jan; 7(1): e2062.

Mesenchymal Stem Cell Treatment for Multiple Sclerosis

Mesenchymal Stem Cell Treatment for Multiple Sclerosis

Multiple sclerosis is a chronic neurological disease that affects the brain and spinal cord. In multiple sclerosis, an immune reaction breaks down the covering around neuronal axons, myelin. Depending on where in the brain or spinal cord this inflammation occurs, patients with multiple sclerosis may experience weakness, a lack of sensation, double vision, difficulty walking, difficulty with balance, problems with urination, dizziness, and/or pain. Over time, patients with multiple sclerosis require assistive devices such as canes or wheelchairs to get around, and some ultimately become bedridden.

Multiple sclerosis can be divided into 4 types:

Clinically isolated syndrome – The first episode of MS; about two-thirds of people with a clinically isolated syndrome of MS will go on to have one of the other types listed below

Relapsing-remitting – Patients have symptoms for a time, which resolve, but then eventually return

Secondary progressive – After some cycles of flare-ups and remissions, the disease is present all the time; some patients with relapsing-remitting disease develop secondary progressive MS

Primary progressive – Once symptoms start, they do not resolve but instead get progressively worse

Fortunately, there are some treatments that can change the course of multiple sclerosis. There are several disease-modifying agents available for people with relapsing-remitting disease and a few for progressive multiple sclerosis. These drugs can reduce the rate at which symptoms get worse or extend the length of time between flare-ups. Unfortunately, not everyone can tolerate these drugs, and, in others, the drugs are not very effective. None of these drugs is a cure for multiple sclerosis.

Researchers have turned to mesenchymal stem cells as a possible treatment for multiple sclerosis. These cells have the ability to regulate the immune system and support the nervous system. There have been so many clinical trials of stem cells in multiple sclerosis that researchers can now perform a meta-analysis on them. A meta-analysis is a special study in which all trials on a particular topic are combined and analyzed, i.e., a study of studies.

In their recent meta-analysis, Dr. Zhou and co-authors identified 9 clinical studies using mesenchymal stem cells to treat multiple sclerosis. They found that the rate of disease progression with stem cell treatment was 16% at 6 months and 35% at 1 year. This is a faster rate of decline than disease-modifying treatment, but better than no treatment at all. Importantly, the MS patients treated with stem cells had much more severe disease than average—it was a group for whom disease-modifying treatment had failed. From this perspective, stem cell treatment for MS was a great success.

Most patients had no evidence of disease activity at 6 months (72%) and 1 year (62%) after autologous mesenchymal stem cell treatment. This a substantial duration of time to be disease-free.

The authors noted that stem cells transplanted via the intrathecal route (i.e. directly in the cerebrospinal fluid) resulted in a slower progression of disability.

Taken together, these results are encouraging. The authors also concluded that mesenchymal stem cell treatment was safe. More work with larger patient groups are needed, but this is an exciting avenue of research.

Reference: Zhou, Y., et al. (2019). Autologous Mesenchymal Stem Cell Transplantation in Multiple Sclerosis: A Meta-Analysis. Stem Cells International. 2019, Volume 2019 |Article ID 8536785.

Treating Chronic Pain with Mesenchymal Stem Cells

Treating Chronic Pain with Mesenchymal Stem Cells

Chronic pain, that is, pain lasting for more than 12 weeks, is extremely common. As many as 1 in 3 Americans struggle with chronic pain, making it perhaps the most common physical condition that afflicts humans. Chronic pain is a source of significant suffering; it makes daily tasks more difficult, limits people’s ability to do the things they enjoy, and greatly diminishes the quality of life.

Perhaps the most frustrating aspect of chronic pain is that there are usually no good treatments. Because the pain is chronic, patients who try to treat chronic pain with medications must take drugs every day. Acetaminophen and non-steroidal anti-inflammatories (NSAIDs) like ibuprofen can help take away some suffering, but they are usually only partially effective. Opioids are stronger, of course, but have such a high risk of causing dependence and addiction that few doctors will prescribe for chronic non-cancer pain. Physical therapy helps some, but not most people. Surgery may be able to treat people with certain types of chronic musculoskeletal pain; however, orthopedic surgery is a major ordeal with no guarantees of success. Consequently, most people with chronic pain are left with very few treatment options.

Perhaps this lack of chronic pain treatment options is what makes recent stem cell research in chronic pain treatment so exciting. Researchers are learning that mesenchymal stem cells appear to be able to treat people with chronic pain. For example, in a study of patients with low back pain who received treatment autologous stem cells (their own stem cell populations purified, expanded, and re-injected in their bodies), their pain and disability decreased to the same levels as people who underwent major orthopedic surgery (spinal fusion or total disc replacement). Another lab in Japan showed similar results.

The same benefit may occur in knee arthritis (osteoarthritis), as well. Researchers showed that autologous stem cells were able to increase the size of the knee meniscus cartilage in a patient with severe knee arthritis. It should be noted that damaged knee meniscus cartilage is one of the main sources of chronic pain in knee osteoarthritis.

Of course, the number of patients treated in these studies is relatively small. Larger studies will be required to confirm that mesenchymal stem cells can treat chronic pain. However, these results are intriguing, since a staggering number of studies show autologous stem cell treatment to be safe. Indeed, mesenchymal stem cell treatment is now widely available in clinics and medical practices.

Reference: Waterman R. et al. (2011). Treating Chronic Pain with Mesenchymal Stem Cells: A Therapeutic Approach Worthy of Continued Investigation. Journal of Stem Cell Research & Therapy. 2011, S2 DOI: 10.4172/2157-7633.S2-001.

Mesenchymal Stem Cell Treatment for ALS is Safe and Feasible

Mesenchymal Stem Cell Treatment for ALS is Safe and Feasible

Amyotrophic lateral sclerosis or ALS is a devastating, progressive neurological disease. While the precise cause is unknown, ALS does destroy nerve cells in the spinal cord, which causes several debilitating symptoms. Often the first symptom of ALS is weakness in the hands or arms that is usually more pronounced on one side of the body. As more spinal cord nerve cells become dysfunctional and die, patients with ALS become weaker, their movements grow slower, and their muscles begin to atrophy (i.e. break down). At the same time, some muscles in the limbs become spastic, which means they are constantly in a contracted state. In later stages of ALS, patients have difficulty swallowing and breathing. Mesenchymal Stem Cell Treatment for ALS is a unique and new option.

The only drug to have any known survival benefit in ALS is riluzole. Patients who take riluzole live longer than those who do not; however, the drug does not improve function or meaningfully reduce symptoms. The only other approved ALS treatment, edaravone, may slow the rate at which ALS gets worse. However, neither of these drugs is a cure—far from it, in fact. Indeed, doctors and patients are left with virtually no effective treatment options for ALS.

Because ALS is caused by the destruction of nerve cells in the spinal cord, the regenerative properties of stem cells may offer a solution. The hypothesis is that stem cells—and exosomes collected from stem cells—can help protect, preserve, or even regenerate cells that are affected by ALS.

A flurry of research has been published over the last decade documenting the safety and possible effectiveness of mesenchymal stem cells for the treatment of ALS. In 2009, Deda et al. showed bone marrow stem cells injected into the spinal area were safe in patients with ALS, even showing that some patients had improvements in neuromuscular testing. The research groups of Karussis, Mazzini, Blanquer, and Baek showed similar safety results. Martinez et al. showed that stem cells derived from bone marrow could improve survival in patients with ALS. Rushkevich et al. showed that stem cell infusion improved the quality of life in patients with ALS.

While more work is clearly needed to determine the full effectiveness of stem cell treatment for ALS, the number of researchers working on this topic and the number of successful studies published in this area are reasons for hope. These clinical studies show that stem cell treatment for ALS is clearly safe and feasible. What is needed are larger clinical trials that specifically focus on the effectiveness of treatment, both in the near- and long-term.

Reference: Roberta Bonafede and Raffaella Mariotti. (2017). Stem cell mobilizers: ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles. Frontiers in Cellular Neuroscience. 2017; 11:80.

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