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Exosomes from Induced Pluripotent Stem Cells Better Than Synovial Membrane Stem Cells Exosomes for Treating Osteoarthritis

Exosomes from Induced Pluripotent Stem Cells Better Than Synovial Membrane Stem Cells Exosomes for Treating Osteoarthritis

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.

 

Exosomes Taken from Stem Cells Help Protect Heart Cells in Heart Attack-Like Conditions

Exosomes Taken from Stem Cells Help Protect Heart Cells in Heart Attack-Like Conditions

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.

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.

Using Stem Cells to Treat Erectile Dysfunction: State-Of-The-Science

Using Stem Cells to Treat Erectile Dysfunction: State-Of-The-Science

Men with erectile dysfunction cannot achieve or maintain an erection suitable for sexual intercourse. Erectile dysfunction can be devastating for the men who suffer from it, putting a strain on intimate relationships, and causing significant emotional suffering. Sadly, half of all men between the age of 40 and 70 experience some degree of erectile dysfunction. Fifteen percent of men are completely impotent, and many men do not respond to typical treatments.

Many men with erectile dysfunction can be successfully treated with phosphodiesterase type-5 inhibitors such as Viagra or Cialis. These pills can be taken daily or as needed to allow men to achieve erections when desired. However, these medications have some significant side effects. For example, these drugs can cause an unsafe drop in blood pressure, especially in people who are taking nitrate medications for heart and cardiovascular diseases. Likewise, these drugs can be expensive, since they are not always covered by insurance programs.

It also should be pointed out, that not all men find success from these erectile dysfunction drugs and must turn to penile injections. Penile injections are particularly inconvenient because an injection must be performed prior to each sexual encounter.

Since most men who suffer from erectile dysfunction have problems with the blood vessel system that makes erections possible, scientists have been investigating the possibility of using stem cells to help regenerate and regrow the cells in that system. While there have only been a handful of clinical trials using stem cells to treat erectile dysfunction, the results are promising.

Bahk and co-authors used umbilical cord stem cells to treat seven men with erectile dysfunction related to their type 2 diabetes. Almost all of the men who received a penile injection of stem cells experienced a return of morning erections and reported an increase in penile hardness. This effect lasted for at least three months after the injection.

Another research group tested adipose (fat tissue) stem cells in men who had erectile dysfunction due to prostate removal surgery. Some of these men also lost their ability to control urine (i.e. urinary incontinence). Eight of 17 men in the trial recovered erectile function. Interestingly, the incontinent men were the ones I the group of 17 who failed to achieve a benefit from stem cell injections.

Lastly, researchers tested stem cells taken from placental tissues (not embryonic stem cells) in men with erectile dysfunction of unknown cause. Men who were treated with stem cells enjoyed a significant increase in blood flow and blood pressure to the penile area. Likewise, several men regained the ability to achieve and sustain erections even though they had been completely impotent before the treatment.

While this research is ongoing, these results are incredibly encouraging for men (and their partners) who struggle with erectile dysfunction. The benefits of stem cells are particularly relevant for men who do not receive any or complete improvement in erectile dysfunction from ED medications. While these treatments do require a penile injection, the effects tend to last much longer than current, non-stem cell penile injections (three months or longer), which is an important innovation and makes treatment far more convenient for patients.

Migraines & MS: What’s the Connection?

Migraines & MS: What’s the Connection?

While migraines have left the medical community puzzled for many years, experts are establishing links among certain conditions which may leave individuals predisposed to them. In specific, recent studies indicated that patients with Multiple Sclerosis (MS) are at least three times as likely to experience migraines, compared to people who do not have the disease. While a concrete explanation for the link has yet to be established, there are some theories which researchers have speculated on.

Reasons for Migraines & MS

One possible explanation for the increase in migraines among MS patients is the fact that MS is at least two to three times more common in women than men, and women are also two to three times more likely to experience migraines compared to men.

Yet, there could be other mechanisms at play. For instance, altered pain perception and threshold could cause a more significant level of pain in patients with MS. And, patients with migraines are more likely to experience additional pain syndromes, including temporomandibular joint (TMJ) pain.

Addressing Migraines in MS Patients

Although the precise mechanisms behind the prevalence of migraines in MS patients may have yet to be identified, patients experiencing migraines can still find relief in the meantime. Since the link is still unknown, most doctors treat migraines and MS as separate entities. In general, most patients respond well to migraine treatments, but it’s also important to consider headache as a potential side effect from medications used to treat MS. In particular, disease-modifying drugs (DMDs) tend to illicit headaches, while as many as 80% of MS patients have described headaches as a symptom after beginning any form of MS therapy.

If you’re experiencing migraines, be sure to discuss the symptom with your doctor. In cases with severe, persistent migraines, expertise from a neurologist may be needed to aid in making informed treatment decisions.

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