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).
Multiple Sclerosis is a disease of the nervous system that involves the demyelination of nerve cells. As nerve cells lose their myelination, it becomes harder for the cells to communicate with one another. Though there are a number of treatment options for multiple sclerosis, which usually involve immunosuppressants, the conventional treatments do not always work over the long-term and may be associated with unwanted side effects. Given the promising results of stem cells being used in treatments for other nervous system diseases, scientists have reasoned that stem cells could provide a valuable therapy for those with multiple sclerosis.
A recent study published in Cytotherapy has demonstrated for the first time the use of neural progenitors derived from bone marrow mesenchymal stem cells. According to the authors of the study, it has previously been recognized that these cells have the potential to help with multiple sclerosis therapy, whether they come from multiple sclerosis patients or those without multiple sclerosis. Preclinical research has also shown that the use of these stem cells can improve disease in multiple sclerosis models and lead to the recruitment of progenitors to sites of inflammation.
In the current study, scientists wanted to establish the safety and dosing of intrathecal neural progenitors derived from bone marrow mesenchymal stem cells in the treatment of multiple sclerosis and investigated the use of these cells in six patients with progressive multiple sclerosis who were not responding to conventional treatments. The patients were treated with between 2 and 5 injections of the stem cells, and they were evaluated for an average of 7.4 years following their first injection.
Not only were there no safety issues that arose with any of the treated patients, but 4 of the 6 patients demonstrated measurable clinical improvement through the use of stem cell treatment. The results of this pilot study provide support for both the tolerability and effectiveness of stem cell therapy for multiple sclerosis. Future research will help to clarify the specific protocols that may be used to achieve the desired results in this group of patients.
Reference: Harris, VK, Vyshkina, T, & Sadaiq, SA. (2016). Clinical safety of intrathecal administration of mesenchymal cell-derived neural progenitors in multiple sclerosis. Cytotherapy, 18(12), 1476-1482.
Mesenchymal stem cells have two unique and powerful properties that make them the focus of intense scientific research. First, mesenchymal stem cells can escape recognition by the immune system. In other words, when mesenchymal stem cells are infused into the body, the immune system does not recognize them as foreign and does not react to them. If the immune system did respond to the stem cells, it would cause an aggressive and potentially deadly allergic or immunologic response. Second, mesenchymal stem cells have the power to inhibit the immune system. This means mesenchymal stem cells could be used to treat immunological and autoimmune diseases such as Rheumatoid Arthritis, Systemic Lupus Erythematosus, Multiple Sclerosis, and Crohn’s Disease, among others. In essence, mesenchymal stem cells can affect the immune system without triggering an inflammatory response making them an ideal treatment for these diseases.
For some time, mesenchymal stem cells extracted from bone marrow were thought to be the only type of mesenchymal stem cells capable of beneficially affecting the immune system. This fact is not necessarily bad, but it does mean that mesenchymal stem cell donors must undergo a bone marrow procedure, which can be painful and expensive. It would be far better if doctors could use mesenchymal stem cells taken from easier-to-get tissues such as fat (adipose), umbilical cord blood, or Wharton’s jelly (umbilical cord tissue). Most people have adequate amounts of fat just under the skin, and umbilical cord blood and tissue are thrown away as medical waste every day.
Fortunately for patients, Dr. Yoo and colleagues showed that mesenchymal stem cells taken from fat tissue, umbilical cord blood, and Wharton’s jelly exhibit the same immunomodulatory properties as mesenchymal stem cells taken from bone marrow. The researchers showed that these types of mesenchymal stem cells were able to suppress T-cell proliferation as effectively as those cells taken from bone marrow. T-cell proliferation, it should be pointed out, is a key step in autoimmune inflammation that occurs in diseases such as rheumatoid arthritis and others.
In short, mesenchymal stem cells taken from easier-to-get tissues were just as effective at suppressing inflammation (in vitro) as those taken from bone marrow. These results will need to be confirmed in clinical studies; however, this approach will be much more convenient and less expensive for patients and donors if they can use mesenchymal stem cells taken from fat or umbilical cord rather than bone marrow and yet reap the same benefits.
Reference: Yoo KH et al. (2009). Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues. Cell Immunology. 2009;259(2):150-6.
The knee is a complex joint that must support the weight of the body while allowing the leg to bend freely. An important part of the knee joint is the meniscus. The meniscus is a fibrous cartilage structure that acts as a shock absorber. While these menisci perform very well during various strenuous activities, they can and do tear. In fact, a torn meniscus in the knee is one of the most common orthopedic injuries.
A torn meniscus of the knee often causes pain and swelling in the knee. Patients with a torn meniscus cannot squat or kneel, and the knee joint does not move smoothly. In fact, many patients with a torn meniscus describe the joint as popping, locking, catching or even “giving out.”
The meniscus of the knee can be torn in several ways; however, most torn menisci result from either one of two things: athletic activity or degenerative arthritis. As you would imagine, menisci torn during sport occur more commonly in young athletes such as dancers, certain kinds of track and field athletes, and basketball, soccer and football players. People with degenerative arthritis tend to be older and often have careers that require a lot of bending at the knee, such as carpet layers, carpenters, plumbers, etc.
Some people can live with small tears in their knee meniscus, but many people ultimately require surgery to fix the problem. One of the major approaches is to perform a total or partial meniscectomy of the damaged knee meniscus. Generally speaking, surgeons offer partial meniscectomy because patients heal faster, and results are about as good as a total meniscectomy. Unfortunately, surgical repair of these tissues is not always successful, especially in older individuals with tears related to degenerative arthritis. Consequently, surgical researchers are keen to discover new ways to improve partial meniscectomy to help people with meniscal tears of the knee.
One exciting option is using stem cells to potentially help patients regrow healthy meniscus after surgeons remove the damaged portion.
In one study, orthopedic surgeons at various surgical centers around the United States participated in an I/II, randomized, double-blind, controlled study to study the effects of human mesenchymal stem cells in people with a meniscal tear of the knee. Researchers recruited 60 patients who were eligible to receive a partial meniscectomy and sorted them into three groups: treatment group A received 50 million human mesenchymal stem cells, group B received 150 million stem cells, and group C (the control group) simply received an infusion of salt water. Patients received an injection of stem cells into the knee, 7 to 10 days after their partial meniscectomy surgery. Then researchers followed the patients for six weeks, six months, one year, and two years after the procedure.
Researchers found that some patients who received human mesenchymal stem cells had a significant increase in the size of their menisci after surgery. By contrast, no single patient in the control group had an increase in the size of their menisci. In other words, stem cells were found to be able to increase the size of the knee meniscus in some patients, as originally hypothesized. Likewise, the study authors could find no clinically important safety issues from injecting stem cells into the knees of patients. Perhaps most importantly, people who received mesenchymal stem cells reported a significant reduction in the amount of pain they experienced due to degenerative changes in the knee. In other words, partial meniscectomy plus stem cells apparently helped patients with degenerative arthritis of the knee.
The authors concluded that this research shows that human mesenchymal stem cells have the potential to be able to repair knee meniscus tissue and improve knee pain in people with meniscal tears. While additional research is needed, these results are very exciting for people who have torn menisci, especially older patients whose knee pain is a result of osteoarthritis or degenerative joint disease in the knee.
Stem cells are generating so much excitement in research and clinical circles because they have the capacity to become many other types of cells. They also release a number of important molecules such as hormones, cytokines, and genetic material that can potentially be helpful for patients. Researchers have found that not only does hyperbaric oxygen therapy (HBOT) help in the circulation of stem cells but it also will help to mobilize stem cells from the bone marrow to the bloodstream further preparing the patient for stem cell therapy.
Bone marrow is a rich source of stem cells, but getting them usually requires an invasive procedure, i.e., placing a large bore needle into the middle of bone(s). Researchers have discovered, however, that hyperbaric oxygen treatment causes stem cells from the bone marrow to move into the bloodstream by specifically stimulating the body’s nitric oxide synthesis. Thus, instead of using a needle to extract stem cells from the bone marrow, patients can potentially increase their own bone marrow stem cells by undergoing hyperbaric oxygen treatment.
Stephen Thom, MD, Ph.D. and co-researchers at the University of Pennsylvania showed that a single hyperbaric oxygen treatment could double the number of bone marrow stem cells in the blood. This means that the hyperbaric oxygen was “mobilizing” the stem cells to move from the bone marrow into the bloodstream to allow them to move into areas of the body that benefit from them. Moreover, when study subjects underwent 20 treatments of hyperbaric oxygen therapy over a few weeks, the number of bone marrow stem cells in the blood increased significantly by eightfold. This astonishing finding has been confirmed in subsequent experiments.
The most important conclusion from this research is that hyperbaric oxygen therapy treatments can unlock the potential of a person’s own bone marrow stem cells without an invasive procedure. While many scientists assumed that the benefits of hyperbaric oxygen therapy were due to the high concentrations of oxygen infusing the blood, tissues, and cells, they now have research to support that these benefits may also be due to stem cell mobilization.
Colitis is inflammation of the colon, also known as the large intestine. Several things can cause colitis such as infection, medication, ischemia, or chronic inflammatory bowel disease. Inflammatory bowel diseases that affect the colon, such as ulcerative colitis or Crohn’s disease, are particularly challenging for patients. It is a chronic disease that causes cramping pain, bloody diarrhea, weight loss, fatigue, and many other chronic, challenging symptoms.
Since ulcerative colitis does not occur naturally in animals, researchers sometimes use an experimental form of colitis to mimic the disease seen in humans. This experimental colitis serves as a model to investigate treatments for inflammatory bowel disease. Essentially, researchers create a situation in which mice develop a condition that looks very much like ulcerative colitis. They develop inflammation in the large intestine, along with signs of oxidative stress and cell death. Conversely, treatments for ulcerative colitis reduce or prevent inflammation, oxidative stress, and cell death in the colon of these experimental mice.
Researchers used this model of experimental colitis to study the effect of bone marrow stem cells as a treatment for colitis. More specifically, they tested the effects of a certain part of bone marrow stem cells called extracellular vesicles. Extracellular vesicles are small spheres that containing various beneficial substances. Stem cells release these vesicles into the body. A single stem cell can release hundreds of extracellular vesicles. In fact, it is the extracellular vesicles that are believed to contain many of the useful substances that are released by bone marrow stem cells such as proteins, lipids, and nucleic acids. These substances can precisely target sick and damaged cells in the body and repair them.
Impressively, when researchers used extracellular vesicles derived from bone marrow stem cells to treat animals with experimental colitis, they observed rather extraordinary results. These vesicles protected the intestines from colitis damage. Untreated animals had severely damaged intestines when viewed under a microscope, but animals treated with extracellular vesicles had nearly normal looking intestines. Treatment also substantially reduced levels of cytokines related to oxidative stress, such as IL-1β. Extracellular vesicles derived from bone marrow stem cells also apparently blocked the intestinal cells’ ability to undergo cell suicide (apoptosis).
Taken together, these results strongly suggest that mesenchymal stem cells from bone marrow, specifically the extracellular vesicles contained within them, can dramatically improve experimental colitis. While more research is needed, this study suggests that these stem cell products could one day be a useful treatment for inflammatory bowel diseases, such as ulcerative colitis and inflammatory bowel disease.