by admin | Jul 12, 2019 | Age Management, Exosomes, Stem Cell Therapy, Umbilical Stem Cell
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.
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.
by admin | Apr 24, 2019 | Exosomes, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Duchenne muscular dystrophy is a degenerative condition that is hereditary caused by mutations to a gene called dystrophin. The condition affects both skeletal and cardiac muscles, impairing physical mobility and leading to weakened heart and respiratory functioning. Current treatments for Duchenne muscular dystrophy aim to control the symptoms of the condition and enhance the quality of life, but there is no known cure.
Given the need for effective therapies in Duchenne muscular dystrophy and the success of stem cells in treating other degenerative conditions, research has begun to focus on how cell therapies may be able to help Duchenne muscular dystrophy patients. Mesenchymal stem cells have been considered as an approach to this form of therapy.
Much of the research to date has emphasized autologous sources of stem cells that come from the patient themselves – such as from bone marrow or adipose tissues. However, a recent study, published in Biomaterials, investigated the impact of allogeneic mesenchymal stem cells – which comes from someone other than the patient – on Duchenne muscular dystrophy. Specifically, the researchers looked at the therapeutic effects of placenta-derived mesenchymal stem cells.
The scientists found that using placenta-derived mesenchymal stem cells may be able to reduce the amount of scarring and thickening of the connective tissue of the cardiac muscles and diaphragm in Duchenne muscular dystrophy while also minimizing inflammation. These promising findings demonstrate the potential to use stem cells to reverse the pathology of Duchenne muscular dystrophy and not just to address the symptoms. Future research will help to determine if regenerative therapy could have a meaningful impact on the course of this condition.
Reference: Bier et al. 2018. Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy. Biomaterials, 174, 67-78.
by admin | Feb 1, 2019 | Adipose, Exosomes, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy, Studies, Umbilical Stem Cell
Most organs of the body recover from injury by generating new, healthy cells. Not every organ of the body has the same ability to form new cells, however. The skin is an example of an organ that has an amazing ability to regenerate. Liver and lung also have the ability to form new cells, but not as dramatically as skin. Kidney and heart have even less ability to repair and regenerate. On the opposite end of the spectrum from the skin is the brain, which has very little capacity to regenerate once it has been damaged or destroyed. All of these organ systems, especially those that are relatively unable to repair themselves, could theoretically benefit from stem cells.
Mesenchymal stem cells, also known as stromal cells, are multipotent stem cells derived from bone marrow, umbilical cord, placenta, or adipose (fat) tissue. These cells can become the cells that make up bone, cartilage, fat, heart, blood vessels, and even brain. Mesenchymal stem cells have shown a remarkable ability to help the body to produce new cells. Researchers are now realizing that the substances stem cells release may be more important than any new cells they may become. In other words, stem cells can directly become new healthy cells to a certain degree, but they can also release substances that dramatically increase the number of new, healthy cells.
Mesenchymal stromal stem cells release small packets called exosomes. These exosomes are filled with various substances that promote cell and tissue growth. Some of the most interesting and potentially useful substances are cytokines and micro RNA. Cytokines are the traffic cops of cellular repair, signaling certain events to take place while stopping others. Having the right cytokines in a particular area is critical for new tissue growth. The micro RNA released by stem cell exosomes is potentially even more exciting than cytokines. These tiny bits of RNA can directly affect how healthy and diseased cells behave. Micro RNA has a powerful ability to control the biological machinery inside of cells.
Exosomes exhibit a wide array of biological effects that promote the repair and growth of damaged and diseased organs. They promote the growth of skin cells and help wounds heal. Exosomes can reduce lung swelling and inflammation and even help the lung tissue heal itself (i.e. reduced pulmonary hypertension, decrease ventricular hypertrophy, and improve lung vascular remodeling). These small packets released by stem cells help prevent liver cells from dying (i.e. prevents apoptosis), promote liver cell regeneration, and slow down liver cirrhosis (i.e. fibrosis). Exosomes can also help protect the kidneys during acute injury and reduce the damage that occurs during a heart attack.
Several clinical trials are underway designed to allow these exciting developments to be used to treat patients. As the researchers state, “Extensive research and clinical trials are currently underway for the use of MSCs as regenerative agents in many diseases including spinal cord injury, multiple sclerosis, Alzheimer’s disease, liver cirrhosis and hepatitis, osteoarthritis, myocardial infarction, kidney disease, inflammatory bowel disease, diabetes mellitus, knee cartilage injuries, organ transplantation, and graft-versus-host disease.” We can reasonably expect that exosomes will be used to treat at least some of these conditions in the very near future.
Reference: Rani al. (2015). Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications. Molecular Therapy. 2015 May; 23(5): 812–823.
by admin | Jan 27, 2019 | Exosomes, Heart Failure, Kidney Disease, Stem Cell Research, Stem Cell Therapy, Stroke, Umbilical Stem Cell
Tissue injury is common to many human diseases. Cirrhosis results in damaged, fibrotic liver tissue. Idiopathic pulmonary fibrosis and related lung diseases cause damage to lung tissue. A heart attack damages heart tissue, just as a stroke damages brain tissue. In some cases, such as minor tissue injury, the damaged tissue can repair itself. Over time, however, tissue damage becomes too great and the organ itself can fail. For example, long-standing cirrhosis can cause liver failure.
One area of active research is to find ways to protect tissue from injury or, if an injury occurs, to help the tissue repair itself before the damage becomes permanent and irreversible. Indeed, tissue repair is one of the main focuses of regenerative medicine. Likewise, one of the most promising approaches in the field of regenerative medicine is stem cell therapy. Researchers are learning that when it comes to protecting against tissue injury and promoting tissue repair, exosomes harvested from stem cells are perhaps the most attractive potential therapeutic.
Why are stem cell exosomes so promising? Exosomes are small packets of molecules that stem cells release to help the cells around them grow and flourish. While one could inject stem cells as a treatment for diseases (and they certainly do work for that purpose) it may be more effective in some cases to inject exosomes directly. So instead of relying on the stem cells to produce exosomes once they are injected into the body, stem cells can create substantial amounts of exosomes in the laboratory. Exosomes with desired properties could be concentrated and safely injected in large quantities, resulting in a potentially more potent treatment for the disease.
Indeed, researchers have shown that extracellular vesicles (exosomes and their cousins, microvesicles) can be collected from stem cells and used to treat a variety of tissue injuries in laboratory animals.
Just a few examples of this research:
- Exosomes from umbilical cord-derived mesenchymal stem cells were able to accelerate skin damage repair in rats who had suffered skin burns.
- Exosomes from the same type of stem cell protected the lungs and reduced lung blood pressure in mice with pulmonary hypertension.
- Exosomes from endothelial progenitor cells protected the kidney from damage caused by a lack of blood flow to the organ.
In this growing field of Regenerative Medicine, research is constant and building as new science evolves from stem cell studies. Researchers are closing in on the specific exosomes that may be helpful in treating human diseases caused by tissue injury.
Reference: Zhang et al. (2016). Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles. International Journal of Molecular Sciences. 2016 Feb; 17(2): 174.
by admin | Jan 25, 2019 | Exosomes, Stem Cell Research
Heart disease is the leading cause of death in the United States, killing over half a million people every year. Heart disease encompasses several conditions and diseases, but the most common causes of deadly heart disease are a heart attack, heart rhythm problems, and heart valve problems. In each of these cases, damaged heart tissue becomes dysfunctional and the heart cannot pump blood efficiently or effectively. To combat this deadly set of diseases, researchers are searching for ways to heal and regenerate heart tissue. Stem cells and stem cell exosomes have shown promise.
While stem cells have been used in a variety of conditions, researchers long doubted the benefit of stem cells in heart disease. The heart, it was believed, was not a “hormonal” organ and thought to be relatively unresponsive to things like cytokines and other messengers. Fortunately, new research has completely changed this viewpoint. According to Drs. Sean Davidson, Kaloyan Takov, and Derek Yellon of the Hatter Cardiovascular Institute in the United Kingdom, “Most, if not all, cells of the cardiovascular system secrete small, lipid bilayer vesicles called exosomes.” The scientists go on to say that exosomes from stem cells “have been shown to be powerfully cardioprotective” and that exosomes produced by stem cells are capable of “activating cardioprotective pathways.”
In simpler terms, the heart and blood vessels are sensitive to the beneficial effects of exosomes. Thus, if exosomes are collected from stem cells, purified and concentrated, and then reinjected into the body, they can repair heart tissue. For example, exosomes collected from mesenchymal stem cells were able to reduce the amount of damage caused by a heart attack in mouse, and improve heart recovery after the event. This could have profound implications for humans who suffer a heart attack since damaged heart tissue can lead to heart failure, heart valve problems, and heart rhythm problems.
The study of stem cells and stem cell exosomes in heart disease is a relatively new science. Clinical trials will need to be performed to determine the role of exosomes in the treatment of heart disease. However, these findings represent an exciting avenue of research in the field of cardiology and regenerative medicine.
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