Exosomes Derived From Umbilical Cord Stem Cells Stimulate Skin Rejuvenation

Exosomes Derived From Umbilical Cord Stem Cells Stimulate Skin Rejuvenation

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.

Umbilical Cord Blood Stem Cell Treatment for Psoriatic Arthritis

Umbilical Cord Blood Stem Cell Treatment for Psoriatic Arthritis

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.

Umbilical Cord as a Source for Mesenchymal Stem Cells

Umbilical Cord as a Source for Mesenchymal Stem Cells

Mesenchymal stem cells are believed by many to be the most effective type of stem cell for regenerative medicine. Mesenchymal stem cells are intriguing because they can regenerate damaged tissues in four major ways:

Paracrine effects – Mesenchymal stem cells release substances that can attract other cells to the site of injury. For example, mesenchymal stem cells secrete cytokines to attract cells that participate in wound healing.

Trophic effects – Mesenchymal stem cells release substances that increase blood vessel development and help cells grow and survive.

Immunomodulation – Mesenchymal stem cells have anti-inflammatory properties, exerting beneficial effects in multiple sclerosis, graft versus host disease, Crohn’s disease, ulcerative colitis, and lupus, among others.

Differentiation – Since they are pluripotent, mesenchymal stem cells have the potential to become other cells such as bone cells, fat cells, brain cells, skin cells, blood vessel cells, and many others.

Unfortunately, it can be difficult to collect mesenchymal stem cells. One major source of mesenchymal stem cells is bone marrow. To collect bone marrow mesenchymal stem cells, however, a person (usually the patient) must undergo a procedure to obtain bone marrow. This procedure is invasive and can be uncomfortable. Therefore, researchers are keenly interested in finding other sources of mesenchymal stem cells.

One very attractive source of mesenchymal stem cells is the umbilical cord. For centuries, umbilical cord tissue was considered medical waste. Once a baby was born and the umbilical cord was cut, the rest of the umbilical cord was usually discarded. Approximately 30 years ago, however, researchers discovered that umbilical cords that were destined to be destroyed as medical waste actually contained cells that could be medically useful. Fifteen years ago, researchers showed that cells taken from umbilical cords contained mesenchymal stem cells that have the ability to become other cells (e.g. fat or bone cells).

Since 2004, researchers have discovered an incredible number of potential uses for mesenchymal stem cells that come from umbilical cord tissue. In fact, research shows that mesenchymal stem cells are taken from discarded umbilical cord actually have higher levels of certain helpful genes then mesenchymal stem cells taken from fat tissue, bone marrow, or skin. Perhaps most impressively, umbilical cord mesenchymal stem cells are non-tumorigenic, which means they do not produce tumors.

Today, mesenchymal stem cells derived from the umbilical cord are the subject of intense clinical research. There are approximately 100 clinical trials testing the safety and effects of umbilical cord mesenchymal stem cells in over a dozen different diseases. In all clinical studies, these stem cells have proven to be remarkably safe—there have been no side effects reported aside from a temporary fever in some cases.

Taken together, these results suggest human umbilical cord is an excellent source of mesenchymal stem cells for several reasons. Unlike embryonic stem cells, there are no ethical problems collecting umbilical cord tissue for stem cells. These particular stem cells appear to be a bridge between prenatal and postnatal mesenchymal stem cells and possess the beneficial properties of each. They do not form tumors, but they do grow in number and become adult cells. As such, human umbilical cord mesenchymal stem cells are unique and are a promising resource in regenerative medicine.

 

 

Reference: Arutyunyan, I. et al. (2017 Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy. Stem Cells International. 2016:6901286.

Allogeneic Stem Cell Therapy for Lupus Nephritis Patients

Allogeneic Stem Cell Therapy for Lupus Nephritis Patients

Systemic lupus erythematosus or simply “lupus” is a chronic inflammatory disease that can affect almost every organ and tissue in the body. Most people are aware of chronic fatigue, muscle and joint pain, and a characteristic facial skin rash that occurs in people with lupus. However, the disease can affect the gastrointestinal tract, lungs, heart, eyes, lymph nodes, and brain. About half of all people with lupus will develop problems in their kidneys related to the disease. The most common kidney problem caused by lupus is a condition known as lupus nephritis.

Lupus nephritis may not cause any outward symptoms, though some patients report foamy urine. Physicians usually detect lupus nephritis during routine urinalysis. Lupus nephritis causes the kidneys to leak substantial amounts of protein in the urine. Over time, this protein loss can cause swelling in the hands, ankles, and feet, and may interfere with kidney function.

The main way in which lupus nephritis is treated is by using strong immunosuppressants such as glucocorticoids (“steroids”; prednisone), cyclophosphamide or mycophenolate mofetil. These immunosuppressing drugs can cause a number of serious and perhaps permanent side effects. Making matters worse, some people with lupus continue to have worsening lupus nephritis even after using these immunosuppressive drugs. In these cases, there is very little that can be done to treat the disease.

In order to help this group of individuals for whom regular treatments did not stop lupus nephritis from progressing, researchers conducted a clinical trial to test the effect of stem cells on this illness. Researchers collected allogeneic mesenchymal stem cells from bone marrow and umbilical cord tissue. They then infused the stem cells in 81 patients with lupus nephritis and followed them for 12 months. Amazingly, 60.5% of patients enjoyed remission of their kidney disease by the 12-month visit. Kidney function (glomerular filtration rate; GFR) significantly improved in patients treated with mesenchymal stem cells. Likewise, total lupus disease activity (not just lupus nephritis) improved significantly 12 months after treatment. These improvements were so profound that patients were able to reduce their doses of prednisone and other immune-suppressing drugs. Importantly, the stem cells did not cause any apparent adverse effects.

If this work can be confirmed in subsequent clinical trials, it is exciting news for patients with lupus, especially those with lupus nephritis. This work suggests that stem cells may be able to reduce the doses of immunosuppressants currently used to treat lupus nephritis, and it may even stop the progression of this terrible illness in some patients. We eagerly await additional clinical research in this area.

 

Reference: Gu F et al. (2014). Allogeneic mesenchymal stem cell transplantation for lupus nephritis patients refractory to conventional therapy. Clinical Rheumatology. 2014 Nov;33(11):1611-9.

Modulating the Immune System with Mesenchymal Stem Cells: Looking Beyond Bone Marrow

Modulating the Immune System with Mesenchymal Stem Cells: Looking Beyond Bone Marrow

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.

Umbilical Cord Mesenchymal Stem Cells Promote Nerve Cell Protection and Blood Vessel Growth

Umbilical Cord Mesenchymal Stem Cells Promote Nerve Cell Protection and Blood Vessel Growth

Much of the initial excitement surrounding stem cells was that they have the potential to become other types of cells. Add cardiac stem cells to a heart damaged by a heart attack, for example, and perhaps those stem cells will become new heart cells and restore heart function. While this does occur—stem cells differentiated mature into adult cells—a fascinating and potentially more exciting use of stem cells is for what they secrete rather than what they become.

Over the past few years, researchers have become increasingly interested in the beneficial substances that stem cells secrete. Researchers refer to the collection of substances that stem cell secretes as its secretome. Stem cell researchers grow various kinds of stem cells in the laboratory and then measure the substances that the stem cells secrete to identify its secretome.

Dr. Hsieh and coauthors discovered that stem cells taken from human umbilical cord secrete an astounding number of helpful molecules. The scientists collected mesenchymal stem cells from Wharton’s jelly (which is a substance found in the human umbilical cord that is normally thrown away as medical waste). They then compared those mesenchymal stem cells with stem cells taken from bone marrow. The researchers found that the umbilical cord mesenchymal stem cells produced molecules that help protect nerve cells, helps nerve cells grow, and help blood vessels grow. The effects were much greater than from cells taken from bone marrow.

One interesting result from their scientific study was the effect of umbilical cord mesenchymal stem cells on injured nerve cells. The researchers deprived brain cells of sugar and oxygen to mimic what the cells would experience during a stroke. The substances secreted by stem cells protected the nerve cells during this harsh treatment. This effect was much stronger in the umbilical cord stem cells compared to the bone marrow stem cells.

Another interesting result from this research was that umbilical cord mesenchymal stem cells helped blood vessel cells organize and form new blood vessels (“tubes”). This could be very important for establishing blood flow to damaged tissue from burns, frostbite, heart attack, or stroke.

These results show that mesenchymal stem cells taken from umbilical cord tissue (Wharton’s jelly) have a unique secretome, which is more potent than similar cells taken from bone marrow. This research is particularly important for patients who have suffered an ischemic stroke or heart attack, as it may provide a clue for a way to treat these conditions in the future.

 

Reference: Hsieh et al. (2013). Mesenchymal Stem Cells from Human Umbilical Cord Express Preferentially Secreted Factors Related to Neuroprotection, Neurogenesis, and Angiogenesis. PLOS One.2013; 8(8): e72604.

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