Using Stem Cells to Treat Musculoskeletal Pain

Using Stem Cells to Treat Musculoskeletal Pain

Virtually everyone will have musculoskeletal pain at some point in their lives. For most, it is a short-lived pain that goes away in a few minutes or a few days. In many, however, musculoskeletal pain is a chronic, daily struggle. They wake up in pain, struggle with pain throughout the day, and pain interferes with their ability to sleep at night.

There are surprisingly few good treatments for chronic musculoskeletal pain. One could take ibuprofen (Advil), naproxen (Aleve), or acetaminophen (Tylenol) to treat short term musculoskeletal pain. However, people with chronic musculoskeletal pain need to take these drugs multiple times a day, every day. Over time, this can damage the liver or the kidneys.

Opioids are powerful painkillers but are not good choices for treating chronic musculoskeletal pain. People who take opioids for more than a few weeks for non-cancer, musculoskeletal pain are at great risk of becoming physically dependent on the drug. Stated another way, they may become addicted to opioids.

Mesenchymal stem cells are an attractive tool to treat musculoskeletal pain because of two main factors. First, they have the ability to find their way to the site of injury and inflammation. In other words, they collect at the site of musculoskeletal pain. Second, stem cells release a large number of substances into the surrounding area that block or reduce inflammation.

Researchers have been making good progress in initial studies of mesenchymal stem cells for various kinds of musculoskeletal pain. For example, people with musculoskeletal pain caused by osteoarthritis of the knee who received stem cells had profound reductions in pain, even great relief the knee debridement surgery (i.e. orthopedic surgery to remove damaged joint tissue and make the joint surfaces smoother. In separate work, Mesenchymal stem cells reduced knee pain improved physical therapy performance and increased the volume of the knee joint affected by osteoarthritis. Similar results have been obtained in people with musculoskeletal pain and osteoarthritis in the hip and foot.

It is important to note that the procedure is safe. In a review of 844 autologous Mesenchymal stem cells infusion procedures for the treatment of osteoarthritis, there were no major adverse events reported.

Musculoskeletal pain is very common. When people develop chronic musculoskeletal pain, it can be debilitating and dramatically diminish the health-related quality of life. While more work is needed, the results detailed here provide hope to the millions of people who struggle with daily musculoskeletal pain.

Reference: Labusca, L. et al. (2015). Stem cells for the treatment of musculoskeletal pain. World Journal of Stem Cells. 2015, Jan 26; 7(1): 96-105.

Bringing Autologous Stem Cell Treatments to the Elderly

Bringing Autologous Stem Cell Treatments to the Elderly

Autologous stem cell treatments offer several advantages over other forms of stem cell treatment. In autologous stem cell treatment, a patient’s own stem cells are retrieved, processed, and injected back into the patient’s body. There is no need for a stem cell donor, and the entire procedure can take place in the same medical office. Since the patient’s own cells are used for an autologous stem cell treatment, there is no risk of disease transmission from a donor (because there is no donor) and no risk of rejection (because they are the patient’s own stem cells).

Unfortunately, younger stem cells are better for regenerative medicine than older stem cells are. Moreover, older people have fewer stem cells that can be harvested than they did when they were younger. So while autologous stem cell treatment is still advantageous, it becomes more difficult to achieve as patients get older because their stem cells are fewer and less potent. Making matters worse, older stem cells compete against more youthful stem cells, making autologous stem cell treatments potentially even less effective in older patients.

Fortunately, stem cell researchers are coming up with ways to make the most out of the stem cells that older patients still have. They still take a sample of tissue, such as fat, and harvest the stem cells contained within it. However, instead of injecting all stem cells from the sample (both older and youthful stem cells), researchers select and use only youthful stem cells. Furthermore, they make the treatments even more effective by injecting other substances (e.g. extracellular matrix) that help youthful stem cells survive, grow, and thrive.

To demonstrate the effectiveness of their approach, researchers collected mesenchymal stem cells from about a dozen older individuals aged 65 to 86 years old. They then assorted the stem cells into different groups, separating youthful from older stem cells. They then used special factors to help the youthful stem cells grow, increasing the numbers by an impressive 17,000 times. So while only 8% of stem cells produced by older individuals are “youthful,” this laboratory process increased those numbers to a point that they can be used for stem cell treatments—even stored for future use!

The next phase of the research will be to inject these youthful stem cells into older patients and assess their effectiveness. However, even these preliminary results are exciting because they suggest that people of all ages can potentially benefit from autologous stem cell treatments, not just middle age and younger individuals.

Reference: Block, TJ et al. (2017). Restoring the quantity and quality of elderly human mesenchymal stem cells for autologous cell-based therapies. Stem Cell Research & Therapy. 2017 Oct 27;8(1):239.

Mesenchymal Stem Cell Treatment for ALS is Apparently Safe and Feasible

Mesenchymal Stem Cell Treatment for ALS is Apparently 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.

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.

Treating Inflammatory Bowel Disease with Stem Cells

Treating Inflammatory Bowel Disease with Stem Cells

Over the past few years, data have accumulated showing the promise for cell-based therapies to help with the treatment of perianal Crohn’s disease. Specifically, stem cells appear to offer the opportunity to overcome several weaknesses associated with conventional therapies that have targeted perianal Crohn’s disease.

Based on these positive results, scientists and healthcare providers have become more adamant about understanding the broader role stem cells could play in the treatment of all inflammatory bowel disease. A new review published in Current Gastroenterology Reports discusses this specific issue and offers insights into the direction of stem cell research as it relates to inflammatory bowel disease.

The authors of this review discuss data from over a dozen clinical trials that have already been conducted on the impact of stem cell therapies in Crohn’s disease. Thus far, much of the success of regenerative medicine for the treatment of Crohn’s disease has been for the specific treatment of perianal Crohn’s disease, which occurs when the digestive and gastrointestinal inflammation associated with Crohn’s disease extends to the anal area.

Given the frequency with which the lining of the intestine is inflamed in inflammatory bowel disease, including both perianal Crohn’s disease and non-perianal Crohn’s disease, research efforts are focusing more and more on how stem cells may be able to combat this type of luminal disease. The authors put forth suggestions for the types of information that researchers should aim to obtain if we are to adequately treat intraluminal disease with regenerative medicine.

The potential of stem cells to address inflammatory bowel disease that has been demonstrated so far provides hope that this type of strategy will help not only patients with perianal Crohn’s disease but those with other forms of inflammatory bowel disease as well. More research should help to determine if and how these therapies can be deployed to help this patient population.

 

 

Reference: Lightner, A.L. (2019). Stem cell therapies for inflammatory bowel disease. Current Gastroenterology Reports, 21(4), 16.

How Bone Marrow Stem Cells Could Help ALS Patients

How Bone Marrow Stem Cells Could Help ALS Patients

Researchers have recently established that a hallmark of Amyotrophic Lateral Sclerosis (ALS) is endothelial cell degeneration that leads to vascular pathology. When this vascular pathology occurs, damage develops to the barrier between the blood and the central nervous system. Given this new understanding of the pathophysiology of ALS, researchers have begun looking at the potential of repairing this barrier as a strategy for treating the disease.

A recent study, published in Scientific Reports, addressed this issue by testing how human bone marrow cells may impact blood-spinal cord barrier repair by transplanting these cells in an ALS model. The researchers hypothesized that the cells should help to repair the barrier, reversing the damage accompanying ALS. They were also interested in whether this type of repair may improve not only the integrity of the barrier between the blood and central nervous system but also improve symptoms of ALS.

What the researchers found was that the human bone marrow cells differentiated into the type of endothelial cells that were needed for repair and successfully engrafted into the capillaries of the spinal cord in their model. Several specific observations led the scientists to conclude that these stem cells helped to effectively restore the barrier between the blood and the spinal cord.

The stem cells improved the integrity and survival of nervous system cells, including astrocytes and spinal cord motor neurons, preventing problematic changes in these cells that are associated with the breakdown of the blood-central nervous system barrier. Critically, the implantation of the stem cells also led to improvements in behaviors associated with ALS.

While there is still a lot of research to be done to establish whether bone marrow stem cells can help repair the blood-spinal cord barrier in patients with ALS, this study provides promising data. Given that there is no cure for ALS and limited treatment options, there is likely to be an emphasis on cell-based therapies for the disease. As more data become available, we will get a clearer picture as to if and how stem cells can help ALS patients.

 

 

Reference: Garbuzova-Davis,S. (2017). Endothelial and astrocytic support by human bone marrow stem cell grafts into symptomatic ALS mice towards blood-spinal cord barrier repair. Scientific Reports, 7(884).

Promising Data for the Use of Stem Cells to Treat Perianal Crohn’s Disease is Accumulating

Promising Data for the Use of Stem Cells to Treat Perianal Crohn’s Disease is Accumulating

Crohn’s disease, a form of chronic inflammatory bowel disease, affects an estimated 700,000 people in the United States, affecting men and women equally. While the disease is characterized by abnormal inflammation in the gastrointestinal and digestive tracts, some people with the illness develop perianal Crohn’s disease. In this case, the inflammation extends to areas around the anus. The precise proportion of Crohn’s disease patients who develop perianal Crohn’s disease is debated, but the need for better treatments for the condition is not.

Unfortunately, though there are several drug and surgical interventions that have been developed to treat perianal Crohn’s disease, each of the available treatment options suffers critical limitations, including risks for adverse side effects.  There is no available therapeutic approach that successfully achieves long-term remission.

Based on the need for – and lack of – more efficacious interventions for perianal Crohn’s disease and the ability of cell-based therapies to address similar types of disease, researchers have positioned that stem cell therapy may be a promising avenue for the relevant patient population. A recent review published in the Journal of Crohn’s and Colitis covers the research that has been conducted to address this possibility and the data that suggest that mesenchymal stem cells could provide a safe and effective way to treat perianal Crohn’s disease without the unwanted side effects associated with conventional treatment options.

In this review, the authors cover clinical trials on cell-based therapies for perianal Crohn’s disease, including phase 1, phase 2, and phase 3 randomized controlled trials. The authors consider the differences in outcomes between conventional treatments and cell-based therapies and offer suggestions for the direction of research into the use of stem cells for the treatment of perianal Crohn’s disease.

 

 

Reference: Lightner, A.L. & Faubion, W.A. (2017). Mesenchymal stem cell injections for the treatment of perianal Crohn’s disease: What we have accomplished and what we still need to. Journal of Crohn’s and Colitis, 11(10), 1267-1276.

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