by admin | Nov 15, 2019 | Adipose, Heart Failure, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
A myocardial infarction, commonly known as a heart attack, occurs when blood flow through the coronary arteries is blocked. A heart attack usually happens to people with atherosclerotic coronary heart disease, which narrows one or more of the coronary arteries. A blood clot becomes lodged in the narrowed artery, preventing blood from reaching the heart muscle. Because the heart needs a virtually constant supply of oxygen-rich blood to survive, an interruption in blood flow to the heart can quickly cause muscle cells to die. There has been much talk in the medical community of using stem cells to rebuild the heart after a heart attack.
Dead heart muscle cells cannot help the heart pump blood. Thus, people who suffer a heart attack are often left with “weak” hearts. Instead of strongly squeezing blood out of the heart to the rest of the body, a larger portion of the blood remains in the heart (i.e. reduced ejection fraction). People who have had a heart attack that reduces ejection fraction commonly develop a condition known as congestive heart failure.
People with congestive heart failure often have difficult lives. Congestive heart failure patients periodically experience exacerbations that require hospitalization. They are put on restrictive diets; their salt and fluid intakes are limited. They must also take several different medications to help the heart pump blood through the arteries to the body and keep fluid levels in the body low. These medications do not heal or replace dead heart muscle cells. Instead, they make the remaining cells work harder (or decrease resistance in the arteries, or help the body eliminate fluid through urination).
What is needed is a way to regenerate dead heart muscle cells. Fortunately, several research groups are working on ways to use stem cells to regenerate heart muscle cells so that heart attack patients can regain heart muscle function.
There have been at least 11 clinical trials studying the effects of stem cells on patients with myocardial infarction. The trials show that stem cell infusion into the vein, the coronary artery, or the heart muscle itself is safe and well-tolerated by patients. Notably among the studies, patients with acute myocardial infarction who received allogeneic human mesenchymal cells intravenously had a better ejection fraction, better heart structure, and better lung function after six months than those who received a placebo. In the APOLLO trial, patients with acute myocardial infarction who received adipose-derived mesenchymal cells had half the dead heart muscle cells than those who received a placebo (i.e. lesion volume was 50% lower in treated patients).
Phase III clinical trials are considered definitive (pivotal) evidence of benefit. In phase III C-CURE trial, patients with heart failure due to coronary artery disease received autologous mesenchymal cells (i.e. their own cells, specially prepared). Treated patients enjoyed significantly increased ejection fraction (heart-pumping ability) and better functional capacity and quality of life. Other Phase II clinical trials (ADVANCE, CONCERT-CHF, TRIDENT, POSEIDON-DCM) are ongoing.
These results are welcome news for patients who suffer—or will one day suffer—from a heart attack, an event that happens in 735,000 Americans every year.
Reference: Golpanian, S. et al. (2016). Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue. Physiological Reviews. 2016 Jul; 96(3): 1127–1168
by admin | Nov 13, 2019 | Stem Cell Research, Exosomes, Mesenchymal Stem Cells
The spinal column is made up of more than a dozen vertebral bones stacked on top of each other. Since the spine is not a single bone, it is capable of pivoting and bending, which gives the torso a degree of flexibility. A key part of this structure relies on the substance between the vertebral bones called the intravertebral disc.
The intravertebral disc is made up of the annulus fibrosis (the tough outer ring) and the nucleus pulposus (the jelly-like inner core). Each intervertebral disc acts as a shock absorber between the vertebral bones. Over time and with age, however, the intervertebral disc tends to breakdown. This can cause called degenerative disc disease, which includes herniated discs (“slipped discs”), pinched nerves, neck and back pain, and nerve problems. Obviously, finding ways to reverse or prevent intravertebral discs from breaking down is of great medical and scientific interest and for the countless patients with degenerative disc disease.
As with other groups interested in regenerative medicine, researchers have turned to stem cells in an effort to regenerate tissue within the intravertebral disc. One research group reported their recent success using bone marrow-derived mesenchymal stem cells. The scientists collected exosomes—very small packets filled with highly concentrated molecules such as proteins, microRNA, transcription factors and lipids—from these stem cells. In this study, researchers also collected exosomes from nucleus pulposus cells and tested the exosomes in various ways.
The researchers found that exosomes could send out signals to bone marrow mesenchymal cells and call them to the intervertebral disc. The exosomes also prompted the stem cells to become new nucleus pulposus-like cells. Conversely, exosomes from bone marrow mesenchymal cells caused nucleus pulposus cells to grow and multiply (i.e. proliferate). Finally, exosomes helped the tissue in degenerating vertebral discs to express the same genes as healthy discs.
While these results are complex, they suggest that exosomes from bone marrow mesenchymal cells and nucleus pulposus cells work together to recruit and make more healthy cells in degenerating vertebral discs. This could have profound implications for the millions of people with degenerative disc disease. If these results are confirmed in clinical trials, it would mean that exosomes could be used to prevent or reverse degenerative disc disease. We anxiously await further work in this exciting field.
Reference: Kang L. et al. (2017). Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells. Stem Cell Research Therapy. 2017; 8: 108.
by admin | Oct 11, 2019 | Mesenchymal Stem Cells, Exosomes, Osteoarthritis
The field of Regenerative Medicine has shown great promise for helping those with a variety of chronic diseases, including arthritis. Indeed, data on the potential value of using stem cells to address issues relating to arthritis have been growing. While specific stem cells like mesenchymal stem cells have demonstrated therapeutic effects in models of arthritis and other inflammatory diseases, the specific ways in which these cells confer their benefits are not yet well understood. Given that these stem cells contain different types of elements, it is important that research establishes which of these elements is critical to the therapeutic properties of stem cells.
A recent study, published in Theranostics, looked specifically at the different effects that small exosomes and larger microparticles from within mesenchymal stem cells have on the inflammatory processes that occur in arthritis. To conduct their experiment, scientists isolated the exosomes and microparticles from mesenchymal stem cells using an ultracentrifugation technique and then exposed the exosomes and the microparticles to cells of the immune system – specifically, T and B lymphocytes, which are implicated in arthritis.
What the researchers found was that, in their models of arthritis, both the exosomes and the microparticles suppressed the T lymphocyte proliferation that is indicative of inflammation. However, unlike microparticles and even parental mesenchymal stem cells, the exosomes were also able to induce other anti-inflammatory effects. The result of exosome activity was, therefore, more efficient blunting of inflammation.
These results point to the potential of not just stem cells, but specifically the exosomes of these cells, in therapeutically addressing inflammatory arthritis. While more research is needed to understand how these exosomes could actually impact arthritis patients, these data provide hope that stem cells and even just elements of stem cells will help these patients by improving their ability to combat problematic inflammation.
Reference: Cosenza, S. et al. (2018). Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis. Theranostics, 8(5), 1399-1410.
by admin | Aug 29, 2019 | Age Management, Mesenchymal Stem Cells, Stem Cell Therapy
Cognitive aging describes the changes to our ability to think, remember, and process information that occurs as we age. Cognitive aging begins in adulthood and progresses—if not accelerates—in old age. Over time, the speed at which we process information in the brain slows down, our ability to pay and maintain attention decreases, and we have a harder time making and recalling new memories. While some view cognitive aging as normal because it occurs in all of us, others acknowledge that cognitive aging is something that interferes with a person’s ability to function and diminishes the quality of life.
Currently, there are very few things that can slow cognitive aging and essentially nothing that can reverse it. Physical exercise, mental activity, and a healthful diet can modestly preserve cognitive function as we age. However, once aging occurs in the brain, there is nothing that we can do—currently—to change it.
Some innovative scientists are trying to change that, however. They are focusing on the changes in the brain that take place during aging and using stem cells to reverse that process.
A group of neuroscientists focused their efforts on memory and on the hippocampus, which is the main region of the brain that is responsible for memory. Researchers collected clinical-grade, mesenchymal stem cells taken from human umbilical cords and infused them into aging mice. Aging mice received stem cell treatment once every two weeks for several months.
After three months of treatment with umbilical cord-derived mesenchymal stem cells, mice showed significant improvement in learning and memory tests. Treated mice also had a remarkably improved function in the hippocampus. Surprisingly, stem cell treatment also created new brain cells (i.e. neurogenesis). Indeed, stem cell transplantation in aging mice actually reversed changes in the brain associated with cognitive aging.
These results were conducted in mice and not in humans, however, this research offers a strong foundation for conducting clinical human studies. If these improvements in memory and brain health could be shown in humans, it would be a groundbreaking study. Even in its current form, this research is an exciting breakthrough for the fields of stem cell medicine, neuroscience, and the neurobiology of cognitive aging. It suggests that mesenchymal stem cells may one day be able to reverse cognitive aging.
Reference: Cao N. et al. (2017). Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse cognitive aging via improving synaptic plasticity and endogenous neurogenesis. 2017 Aug 10;8(8):e2996.
by admin | Jul 29, 2019 | Exosomes, Mesenchymal Stem Cells
Periodontal disease, better known as gum disease, is very common. About half of all adults have chronic gum disease, and as many as 15% had severe periodontal disease. In periodontal disease, the gums become red and inflamed. The tissues that connect the tooth to the bone, such as the periodontal ligament, are damaged or destroyed. Chronic periodontal disease can even invade and destroy jaw bone. Making matters worse, as the gums recede, they can collect bacteria in spaces called periodontal pockets. Over time, these periodontal pockets can become dental abscesses. As the gums become more and more diseased, the affected tooth or teeth may fall out.
The treatment for periodontal disease varies depending on its severity. Good oral hygiene including regular brushing and flossing can reverse mild periodontitis. A dentist can deeply clean, probe and disrupt periodontal pockets. In more severe cases, topical antiseptics or oral antibiotics may be required. Less often, a dental surgeon must remove diseased areas of gum and bone.
Periodontitis usually chronic and causes significant ongoing inflammation. Thus, the gums take a long time to heal. In many cases, periodontal disease can be difficult to treat.
Fortunately, dental researchers have been exploring ways to use mesenchymal stem cells to help the healing process. More specifically, they have been using the exosomes released by mesenchymal stem cells. Exosomes are small packets of proteins, RNA, and other molecules that help promote growth and tissue regeneration. Since exosomes are not cells, they are much easier to collect, store, transport, and administer to patients. Most importantly, exosomes appear to contain all of the things that make stem cells so powerful in regenerative medicine.
In a 2019 study, Dr. Chew and colleagues used exosomes collected from mesenchymal stem cells to treat rats with periodontal disease. The researchers noticed that animals treated with exosomes healed much faster than untreated animals. Exosomes taken from mesenchymal stem cells promoted periodontal tissue regeneration helped grow new bone and regrew periodontal ligaments. The researchers also found that exosomes were able to recruit new cells to replace the damaged ones.
This scientific research is an exciting breakthrough in the fields of dentistry and periodontics. Chew and co-authors have shown that mesenchymal stem cell exosomes could enhance periodontal tissue regeneration without any adverse effects. The scientists go on to state that these findings will serve as the basis for future “cell-free” exosome treatments for periodontal disease. This is certainly good news for the more than 150 million Americans with periodontitis.
Reference: Chew, JRJ. et al. (2019). Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration. Acta Biomaterialia. 2019 Apr 15;89:252-264.
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.
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