The little blue pill brought erectile dysfunction from out of the shadows and into our shared awareness. Erectile dysfunction affects millions of men and, in turn, their sexual partners. The condition can undermine a man’s sense of self-worth, self-esteem, and masculinity. While the little blue pill has been instrumental in getting men with erectile dysfunction to ask their doctors about treatment, that same pill does not work for every man. Indeed, countless men fail to achieve successful erections even after taking oral erectile dysfunction medication.
In one of the first clinical studies of its kind, urologists at a medical practice in Florida tested the effects of mesenchymal stem cell treatments in men with erectile dysfunction. They selected eight men with erectile dysfunction who could not achieve erections even after oral medications. The men received mesenchymal stem cells that were derived from human placenta (also known as afterbirth). The urologists then followed the men for six months after treatment, testing blood flow, penile size, and erectile function.
The men treated with mesenchymal stem cells had a statistically significant increase in penile blood flow at six weeks, three months, and six months after treatment. Three men were able to achieve erections within three months of treatment without oral erectile dysfunction medication. After stem cell treatment, four other men were able to achieve erections with low-dose oral erectile dysfunction medication (which had previously been ineffective).
Importantly, the treatment was well-tolerated by all men in the study, which is an important milestone for continuing this research.
The study is potentially groundbreaking as it opens the door to larger clinical studies in men with erectile dysfunction. Indeed, nearly two dozen clinical trials are now studying the effects of stem cell treatment for erectile dysfunction. These early results are exciting, and offer hope to men with erectile dysfunction, especially those for whom oral medications have failed.
Reference: Levy, JA (2016). Determining the Feasibility of Managing Erectile Dysfunction in Humans With Placental-Derived Stem Cells. The Journal of the American Osteopathic Association. 2016 Jan;116(1):e1-5.
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.
As we age, the appearance and structure of our skin changes. This is plain for all to see—we can usually estimate a person’s age simply by looking at their skin. Young skin is full of molecules that keep it thick, plump, and supple, such as collagen and elastin. Over time, the skin produces less and less of the substances. Consequently, aging skin is thinner and it loses its strength and elasticity. As such, the skin develops fine lines and deep wrinkles. It also becomes lax and begins to sag.
Scientists know that the quantity of collagen, elastin, and other proteins make the difference between young and old skin. Not surprisingly, doctors have been trying for decades to increase the levels of these molecules in the skin in an effort to reverse the signs of aging skin. Some approaches work for short periods of time. For example, laser and intense pulsed light treatments can stimulate the skin to produce these youthful molecules. Another approach is to directly inject collagen and other substances into the skin. The Holy Grail of skin rejuvenation, however, is to find a way to make the skin naturally produce more of these substances. Recent research suggests that stem cells could be the answer.
Researchers collected mesenchymal stem cells from umbilical cords. This tissue is removed and discarded after a woman gives birth to a baby. The scientists then collect the tiny sacs called exosomes from these umbilical cord stem cells. Exosomes are densely packed with proteins, RNA, and other important molecules that are important for growth in rejuvenation. The researchers then simply applied these exosomes to samples of human skin to see if they could influence skin rejuvenation.
The first remarkable finding of this research was that exosomes taken from umbilical cord mesenchymal stem cells were absorbed into human skin. Why is this important? Because it means that if exosomes are used as a potential treatment, they can be placed on the skin rather than injected into the skin. The second remarkable finding is that exosomes, once they cross into the skin, are taken up by skin cells (human dermal fibroblasts). Once inside the skin cells, the exosomes take over the cells, in a way. They prompt the cells to produce more collagen and elastin than normal. The exosome-treated skin cells also attract other cells to the skin. We know from other work that more collagen, more elastin, and more cells within the skin leads to plumper, fuller, more elastic skin.
While clinical trials are needed to confirm this research, this work strongly suggests that the exosomes from umbilical cord-derived mesenchymal stem cells have the ability to rejuvenate human skin. Perhaps most impressively, these potential skin rejuvenating exosomes can be applied topically, such as within a cream or ointment. Thus, patients could receive the potential benefits of this treatment, while avoiding painful injections. Again, more work needs to be done before this research becomes a routine treatment, but the results are quite promising.
Reference: Kim, YJ. et al. (2017). Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate rejuvenation of human skin. Biochemical and Biophysical Research Communications. 2017 Nov 18;493(2):1102-1108.
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.
A heart attack is a life-threatening event in which blood flow through a coronary artery—and blood flow to the heart muscle itself—stops. If that blood flow is not quickly restored, heart muscle dies. A heart attack can be deadly if the heart is too badly damaged.
If someone experiences a heart attack, the heart muscle may be permanently weakened. Instead of having heart muscle that contracts to pump blood, the damaged heart tissue becomes full of fibers (fibrotic tissue) and is basically useless.
Regenerative Medicine has allowed scientists to reconsider whether this fibrotic tissue is permanently lost. Can stem cells prevent this fibrotic tissue from developing? Can new, healthy heart muscle be formed in its place? Recent research offers some tantalizing clues.
Researchers set out to determine whether mesenchymal stem cells taken from human umbilical cord could protect heart muscle cells (cardiomyocytes) after a heart attack. Specifically, the researchers were interested in learning whether exosomes collected from those stem cells (rather than the stem cells themselves) could protect cardiomyocytes.
To test this hypothesis, they created a heart attack in laboratory rats and administered exosomes they had gathered from mesenchymal stem cells. These particular mesenchymal stem cells were collected from human umbilical cord samples—the tissue that is normally thrown away after a baby is born.
The results of these experiments were interesting for several reasons. First, stem cell exosomes tipped the balance between fibrotic tissue (fibroblasts) and heart tissue (myofibroblasts). In other words, after an experimental heart attack, exosomes caused the heart to regrow more normal tissue than diseased tissue. Second, exosomes decreased the inflammation that occurs after a heart attack. It is believed that inflammation makes a heart attack worse. Lastly and perhaps most importantly, exosomes protected cardiomyocytes (heart muscle cells) from dying (through apoptosis).
Taken together, these results suggest that exosomes collected from umbilical cord mesenchymal stem cells protect heart muscle cells from the damaging effects of a heart attack in at least three important ways.
As these are early in Regenerative Medicine research, it is important to note that these experiments were performed in rats, and not humans. Interestingly, though, the stem cells were taken from human umbilical cords, and they were able to achieve these impressive effects in a different species (rodents). Obviously clinical trials are needed to determine whether this effect is applicable in humans; however, studies that use whole stem cells from human umbilical cord strongly suggest scientists are on the right track.
Reference: Shi, Y. et al. (2017). Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Promote Fibroblast-to-Myofibroblast Differentiation in Inflammatory Environments and Benefit Cardioprotective Effects. Stem Cells and Development. 2019 Jun 15;28(12):799-811.
Psoriatic arthritis is a chronic inflammatory condition that can become profoundly disabling. As a form of arthritis, the condition causes swollen, painful joints. The number and types of joints affected can vary over time, but most patients have polyarthritis i.e. arthritis in more than one body joint. Psoriatic arthritis also causes debilitating inflammation of the tendons, typically in the hands. Making matters worse, patients with psoriatic arthritis also suffer from skin rashes, eye problems, kidney and gastrointestinal problems, and profound fatigue. About one in five patients with psoriatic arthritis eventually develop severe manifestations of the disease in which the joints become permanently deformed and the surrounding bone breaks down.
The treatment of psoriatic arthritis usually includes a combination of drug and non-drug treatments. Nondrug treatments for psoriatic arthritis include exercise, physical therapy, and weight loss. Mild psoriatic arthritis is usually treated with nonsteroidal anti-inflammatory drugs such as naproxen. Moderate to severe psoriatic arthritis generally requires disease modifying anti-rheumatic drugs (DMARDs), which can include biologic and non-biologic agents. The typical non-biologic treatment for psoriatic arthritis is methotrexate. With the exception of severe disease, most physicians try methotrexate before using a biologic DMARD. If methotrexate fails, patients usually must move to one of the biologic agents, antibodies that are injected under the skin. Unfortunately, all DMARDs are associated with certain and sometimes severe side effects, and not every DMARD works for every patient with psoriatic arthritis.
Because psoriatic arthritis is potentially disabling and often difficult to treat effectively, researchers are aggressively pursuing other treatments. Stem cells offer a unique opportunity to provide patients with cells that can regenerate damaged joints and reverse the signs and symptoms of arthritis. To this end, Margaret Coutts and colleagues harvested stem cells from umbilical cord samples—the tissue that is routinely corrected after newborns are delivered is usually discarded as medical waste. They selected a patient with severe psoriatic arthritis would fail to find relief after nonsteroidal anti-inflammatory drugs, methotrexate, and biologic DMARDs. The researchers purified stem cells from cord blood and administered 200,000 cells per day to the 56-year-old man over a period of five days.
Within one week of umbilical cord stem cell treatment, the patient reported fewer and less severe psoriatic skin plaques and less joint pain. Encouraged by these results, the psoriatic arthritis patient continued receiving three rounds of stem cell treatments over six months. At the end of these treatments, the psoriatic skin plaques were almost completely gone, and the ones that remained were smaller, less prominent, and lost their red, scaly appearance. The man had substantially less joint pain and swelling and reported feeling “higher energy levels” and greater physical functioning. Lastly, laboratory markers of inflammation including ESR and CRP were noticeably improved.
Since these dramatic improvements occurred for only one person, they should be evaluated with caution. Additional studies with larger numbers of people are needed to make definitive conclusions. Nevertheless, umbilical cord stem cells led to profound improvements in this psoriatic arthritis patient’s life, a result that cannot be overstated.
Reference: Coutts, M. et al. (2017). Umbilical cord blood stem cell treatment for a patient with psoriatic arthritis. World Journal of Stem Cells. 2017 Dec 26; 9(12): 235–240.
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