by admin | Sep 24, 2019 | Adipose, Stem Cell Research, Stem Cell Therapy
Crohn’s disease is a chronic illness that can affect any part of the gastrointestinal tract but mostly affects the small and large intestines. People with Crohn’s disease often have inflammation of the large bowel (Crohn’s disease is an inflammatory bowel disease or IBD). This colitis causes abdominal pain, cramping, diarrhea, along with bleeding and infections in the gastrointestinal tract. Crohn’s disease can interfere with a person’s ability to absorb nutrients, leading to malnutrition and weight loss. The medical community is debating whether it is possible to treat experimental colitis with fat-derived stem cells.
The standard medical treatment for Crohn’s disease involves one or more powerful drugs. When the disease flares up, patients usually must take steroids either orally or intravenously. They may also receive disease-modifying therapy such as immunomodulators and biologic medications. Many patients do enjoy remission once they receive these powerful drugs; however, side effects can be difficult to tolerate. Patients who cannot tolerate these powerful drugs or do not achieve disease remission may have to take steroids every day. Chronic steroid use has many severe and sometimes permanent side effects. If these treatments fail, patients may need to have surgery to remove a portion of their intestines that have been damaged by Crohn’s disease.
In an effort to find safe and effective treatments for Crohn’s disease, researchers have been testing stem cells in laboratory animals. In one study, scientists used a chemical to cause colon inflammation (colitis) in mice. This chemical causes many of the symptoms of humans with Crohn’s disease experience such as diarrhea, tissue damage, and weight loss. The researchers then treated some of the mice with mesenchymal stem cells gathered from human fat tissue (adipose) to see if stem cells could improve the symptoms.
Remarkably, human stem cell treatment reduced diarrhea, inflammation, and disease severity in mice with colitis. The chemical colitis caused mice to lose approximately 15 to 20% of their body weight. Mice that received stem cell treatment regained most of the weight they had lost. Researchers also noted that mice treated with adipose-derived mesenchymal stem cells lived significantly longer than those that did not receive stem cell treatment.
Of course, this research was performed in laboratory animals, but it lays important groundwork for testing in humans. Indeed, since the publication of this report, researchers have been able to show that adipose-derived stem cells helped patients with Crohn’s disease. This exciting work will no doubt lead to future studies that may help pave the way to wider use of stem cells in the treatment of inflammatory bowel disease, such as Crohn’s disease.
Reference: Gonzalez, M. (2009). Adipose-Derived Mesenchymal Stem Cells Alleviate Experimental Colitis by Inhibiting Inflammatory and Autoimmune Responses. Gastroenterology. Volume 136, Issue 3, March 2009, Pages 978-989
by admin | Sep 20, 2019 | Parkinson's Disease, Progressive Supranuclear Palsy, Stem Cell Research, Stem Cell Therapy, Supranuclear Palsy
Progressive supranuclear palsy, also known as PSP, is a disorder of the brain that gets worse over time (progressive neurodegenerative disorder). Many progressive supranuclear palsy symptoms are similar to Parkinson’s disease. These include rigidity, slowness of movement, cognitive (thinking) problems, difficulty speaking, and difficulty swallowing. While people with Parkinson’s disease can have an unsteady gait and “freeze,” these symptoms are much more prominent in people with progressive supranuclear palsy. Likewise, people with PSP have a particular eye problem called supranuclear gaze palsy, which causes PSP patients to have difficulty moving their eyes in certain directions.
Despite the similarities between PSP and Parkinson’s disease, there are no treatments for progressive supranuclear palsy as they are for Parkinson’s disease. Drugs like levodopa help reduce tremors and rigidity in people with Parkinson’s, but they have been largely ineffective in people with PSP. Some PSP patients may benefit from drugs like levodopa, but most experience severe visual hallucinations or other side effects, which causes them to stop the medication. Because there are so few treatments, patients with progressive supranuclear palsy rely on supportive care measures such as occupational and physical therapy, nutritional support, and palliative care.
To address this critical need, researchers are testing mesenchymal stem cells for their ability to treat progressive supranuclear palsy. Dr. Margherita Canesi and her colleagues selected five patients with progressive supranuclear palsy. Her research team used bone marrow from healthy volunteers to select healthy mesenchymal stem cells. The researchers then infused the mesenchymal stem cells into patients in a single infusion.
While patients with PSP normally deteriorate rapidly, the patients who received a single stem cell treatment remained stable for at least six months after treatment. Some patients still maintained function at the end of the study (12 months). All patients tolerated the treatment well, there were no major side effects. While the study was small, it suggests that stem cell treatment was able to change the natural course of the disease. Based on these encouraging results, the authors have set their sights on a randomized, placebo-controlled phase 2 study to further test mesenchymal stem cell treatments in patients with progressive supranuclear palsy. We look forward to their results with great enthusiasm.
Reference: Canesi, M. et al. (2016). Finding a new therapeutic approach for no-option Parkinsonisms: mesenchymal stromal cells for progressive supranuclear palsy. Journal of Translational Medicine. 14, Article number: 127 (2016).
by admin | Aug 19, 2019 | Exosomes, Stem Cell Research, Stem Cell Therapy
Given the limitations of several conventional methods to treat a wide variety of diseases and injuries, stem cell therapy has begun to gain in popularity. The evidence supporting the field of Regenerative Medicine, which involves using stem cells to regenerate healthy, functional tissue, has indeed been accumulating in recent years.
There are a number of different types of stem cells that have been explored for their therapeutic potential. Mesenchymal stem cells have become a preferred option for therapy because of their ability to differentiate into several different types of adult tissue and to be transplanted safely and effectively into patients.
One-way mesenchymal stem cells confer their therapeutic benefits is through paracrine effects that are achieved by the secretion of extracellular vesicles, some of which are exosomes. Exosomes are between 30 and 100 nanometers (nms) in diameter and exist in blood, cerebrospinal fluid, and other bodily fluids.
A recent review, published in Cell Transplantation, covered research showing that mesenchymal stem cell exosomes are therapeutically advantageous for the management of several conditions, including Parkinson’s disease, osteoarthritis, and stroke.
The review discusses, for instance how in models of Parkinson’s disease, exosomes have been shown to provide neuroprotection. MSC-derived exosomes also appear to inhibit inflammation in the context of osteoarthritis and also to stimulate repair in damaged tissue. Further, specific exosome biomarkers, miR-9 and miR-124, have proven to be promising in diagnosing the severity of stroke.
Based on recent research covered in this review, stem cell-derived exosomes have significant therapeutic potential. Though this review focuses specifically on the relevance of exosomes in Parkinson’s disease, osteoarthritis, and stroke, exosomes will likely provide benefits for patients in a variety of contexts and will prove to be an important part of Regenerative Medicine.
Reference
Chang, Y-H, et al. (2018). Exosomes and stem cells in degenerative disease diagnosis and therapy. Cell Transplantation, 27(3), 349-363.
by admin | Jul 25, 2019 | Age Management, Mesenchymal Stem Cells, Stem Cell Research
Aging skin goes through a number of predictable changes. Skin loses collagen and other proteins as it ages, making the skin appear dull, saggy, discolored, and wrinkly. Many of these changes are due to the sun, as it bombards the skin with harmful ultraviolet (UV) radiation. When the skin is exposed to the sun’s UV radiation, it produces reactive oxygen species and leads to oxidative stress. The result is of these oxygen radicals is thickened, damaged, photo-aged skin. Unfortunately, the cells that could help replenish and rejuvenate the skin—epidermal progenitor cells—may also be damaged by UV radiation. Indeed, as we age, we produce fewer and fewer of these helpful cells. Thus, the skin is left defenseless.
Researchers are looking for ways to fight back against the ravaging effects of age and sun damage on human skin. Some have reasoned that if the skin lacks epidermal progenitor cells during aging, why not try to protect or restore those cells? Consequently, some scientists have studied the effects of injecting stem cells directly into the skin (with promising results). However, many patients would like to have the same skin rejuvenation effect without painful injections. Scientists are learning that the beneficial effects of stem cells come mostly from the things that they secrete rather than the stem cells themselves. This means that doctors could potentially take the fluid that a stem cell secretes and use that liquid as a treatment, rather than injecting whole stem cells into a patient’s skin. Indeed, this is the approach that researchers recently pursued and published.
Researchers began their research by collecting epidermal progenitor cells taken from mesenchymal stem cells. These epidermal progenitor cells are the stem cells that give rise to skin. Epidermal progenitor cells also produce substances that help support natural, youthful skin growth and development. The researchers allowed these epidermal progenitor cells to produce and release substances into the surrounding solution. They then collected that solution and used it in subsequent experiments.
In the first set of experiments, researchers showed that the cell-free fluid derived from stem cells could protect skin cells from oxidative stress caused by hydrogen peroxide. Indeed, something (or things) released by the stem cells prevented skin cells from undergoing the types of changes they would endure during sun damage. In fact, the treatment apparently caused the skin to increase its own natural defenses by producing more antioxidant enzymes and increasing the creation of new collagen.
Encouraged by these results, the researchers then conducted a clinical study of 25 people between the ages of 29 and 69. They took the same cell-free fluid derived from stem cells and applied it topically to the skin of volunteers twice a day for four weeks. The treatment significantly reduced skin depressions and wrinkles. Treatment also noticeably improved the texture of the skin.
Given the apparent safety and efficacy of this cell-free treatment, researchers are likely to continue to test these treatments in larger clinical trials. The results are exciting because they offer the possibility of a topical stem cell treatment without directly injecting stem cells themselves. Indeed, patients may someday be able to use cell-free stem cell skin rejuvenation treatments at home.
Reference: Sohn, SJ. et al. (2018). Anti-aging Properties of Conditioned Media of Epidermal Progenitor Cells Derived from Mesenchymal Stem Cells. Dermatology and Therapy. 2018 Jun;8(2):229-244.
by admin | Jul 16, 2019 | Spinal Cord Injury, Stem Cell Research
Though spinal cord injury is relatively common, with the incidence continuing to grow, there is only one medication used to treat this injury, and it is limited in its effectiveness. Methylprednisolone also comes with serious health risks and must be employed in a short 8-hour therapeutic window.
Given the successes observed with stem cell treatments for other nervous system injuries and diseases, scientists have posited that stem cell therapy could offer new opportunities to help those with spinal cord injury. As such, researchers recently conducted a study to determine whether a certain type of stem cell has the potential to treat spinal cord injury and whether that treatment would be safe to use in patients. The results of the study were published in The Journal of Spinal Cord Medicine.
In their study, the scientists used what is referred to as intrathecal transplantation of autologous adipose-derived mesenchymal stem cells, which are stem cells that come from fat tissue. They used these stem cells in 14 patients with spinal cord injury and evaluated the impact of these stem cells on the nervous system and on motor performance, and also monitored patients for any unwanted side effects.
Researchers did not see significant changes in magnetic resonance imaging (MRI) results over the 8 months following stem cell transplantation, but they did observe improvements in motor scores, suggesting that the stem cells were therapeutically effective against spinal cord injury. Importantly, the intrathecal transplantation of stem cells in these patients was not associated with any serious adverse events. Based on these results, scientists recommend that stem cell protocols are further investigated for their potential to treat patients with spinal cord injury.
Reference
Hur, JW et al. (2016). Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial. The Journal of Spinal Cord Medicine, 39(6), 655-663.
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.
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