Stem Cells Improve Physical Health and Stamina in Elderly Patients

Stem Cells Improve Physical Health and Stamina in Elderly Patients

Frailty is a syndrome of weight-loss, exhaustion, weakness, slowness, and decreased physical activity. These features combine to make frail individuals more susceptible to physical, psychosocial, and cognitive impairments. Unfortunately, frailty is rather common among elderly individuals. In one study of over 44,000 elderly adults living in the community estimated the overall prevalence of frailty was 10.7%. While the risk of becoming frail increases with old age, frailty is not a normal part of aging. Instead, the syndrome of frailty is driven by biological processes such as inflammation and stem cell dysfunction.

No specific treatment can prevent or reverse frailty. Indeed, the goal of treatment is to maximize the patient’s functional capacity and overall health. The most widely accepted way to manage frailty is a multimodal and multidisciplinary approach. Frail individuals or those at risk for becoming frail are encouraged to participate in strength training and aerobic exercise to build up a cardiovascular reserve and physical fitness. At the same time, substantial efforts are devoted to helping patients consume enough calories to maintain lean muscle and support their immune function. As appetite diminishes, malnutrition can become an issue, so supplemental nutrition may be needed. Physicians can help patients by optimizing medical treatments and reducing the total number of medications prescribed (i.e. avoiding polypharmacy).

Despite these multimodal treatments, most frail patients tend to get worse over time. One hope of treatment is to slow the rate of decline; however, this is not always possible.

Since frailty is driven by stem cell dysfunction, a reasonable way to prevent or treat frailty could be to provide patients with healthy stem cells. Researchers recently conducted a randomized, double-blind, clinical trial in 30 elderly patients with frailty. Frail patients received an IV infusion of either human mesenchymal stem cells or placebo. The researchers then followed the patients for 6 months to assess the safety and efficacy of the stem cell treatment.

Stem cell treatment resulted in a rather remarkable set of benefits for frail patients. Compared to placebo, patients treated with stem cells performed significantly better on tests of physical strength and stamina. Stem cell-treated patients used calories more efficiently, which is a sign that they were more physically fit than those in the placebo group. Moreover, patients who received stem cells had better lung function at the end of the trial than those in the control group. Interestingly, women who received stem cell treatment reported a substantial increase in sexual quality of life compared to those in the placebo group. Lastly, no patients experienced any treatment-related serious adverse events.

When one considers how difficult it is to treat frailty or even alter its progressive decline, these results are remarkable.  Stem cell treatment not only stopped the progression of frailty, but patients actually improved in several important measures including physical strength, physical endurance, lung function, and sexual quality of life. We anxiously await a pivotal clinical trial to confirm these results.

 

 

Reference: Tompkins, BA. (2017). Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. The Journals of Gerontology, Series A, Biological Sciences and Medical Sciences. 2017 Oct 12;72(11):1513-1522.

Stem Cell Facial Therapy Rejuvenation with Derived Cream

Stem Cell Facial Therapy Rejuvenation with Derived Cream

You don’t need a microscope to recognize aging skin. Aging skin has fine lines and wrinkles; it sags because it has lost elasticity; it is discolored and blotchy. But if you did look at aging skin under a microscope, you would notice that it lacks collagen, elastin, and many other helpful proteins. There would be many old cells and a few young ones. Indeed, old skin looks different under a microscope than new skin, and it is these differences at the cellular level that causes the aging we see on people’s faces. Stem cell facial therapy may be an option for one seeking to improve or prevent the signs of aging.

Fortunately, these cellular changes may not be a curse. Stem cell therapy may be able to replace the proteins that are lost during aging and replace old cells with newer, healthier cells. In short, stem cell facial therapy may be able to can rejuvenate skin and reverse the signs of aging.

The team of Korean stem cell researchers recently completed a study in which they collected mesenchymal stem cells from various sources and used them to rejuvenate human skin. The researchers collected stem cells from fat tissue (adipose), bone marrow, and umbilical cord samples. Umbilical cord tissue is tissue that is normally discarded after childbirth as medical waste. In the laboratory, the scientists then cleaned and purified each of these types of mesenchymal stem cells.

In laboratory studies, the researchers found that mesenchymal stem cells produced substantial amounts of skin rejuvenating factors including collagen type I, collagen type IV, fibronectin, and elastin. Interestingly, they found that umbilical cord mesenchymal stem cells produced a 100-fold greater amount of GDF-11 than adipose or bone marrow stem cells. This is important because GDF-11 is a cytokine that stimulates the production of collagen and elastin. GDF-11 also attracts human dermal fibroblasts (i.e. healthy skin cells) that then, in turn, produce their own collagen and elastin. These substances make skin healthy, elastic, vibrant, plump, and full.

Given the remarkable amounts of GDF-11 that umbilical cord-derived stem cells produced, the researchers decided to conduct a clinical trial to test the effect of these cells on aging skin. The scientists created a cream that contained the substances produced by the stem cells, including exosomes and beneficial proteins. The women who volunteered for the study applied the cream to their faces once per day. Within 2 to 4 weeks, the women had increased skin density (i.e. thickness/fullness) and substantially reduced wrinkles, especially around the eyes. Moreover, treatment with the stem cell-derived cream did not cause irritation, stinging, or any other adverse reaction.

This clinical study will need to be repeated in larger numbers of volunteers; however, the results are quite remarkable. Researchers were able to collect stem cells from umbilical cord tissue and prepare a cosmetic that reversed some of the signs of facial aging. Conveniently, this treatment did not require injections but could be applied topically. If future research confirms this work, treatment with a cosmetic/cosmeceutical made from umbilical cord stem cells could be a painless way to achieve facial skin rejuvenation.

 

 

Reference: Kim, YJ. (2018). Conditioned media from human umbilical cord blood-derived mesenchymal stem cells stimulate rejuvenation function in human skin. Biochemistry and Biophysics Reports. 2018 Oct 25;16:96-102.

Researchers Effectively Treat Experimental Colitis with Fat-Derived Stem Cells

Researchers Effectively Treat Experimental Colitis with Fat-Derived Stem Cells

Crohn’s disease is a chronic illness that can affect any part of the gastrointestinal tract but mostly affects the small and large intestines. People with Crohn’s disease often have inflammation of the large bowel (Crohn’s disease is an inflammatory bowel disease or IBD). This colitis causes abdominal pain, cramping, diarrhea, along with bleeding and infections in the gastrointestinal tract. Crohn’s disease can interfere with a person’s ability to absorb nutrients, leading to malnutrition and weight loss. The medical community is debating whether it is possible to treat experimental colitis with fat-derived stem cells.

The standard medical treatment for Crohn’s disease involves one or more powerful drugs. When the disease flares up, patients usually must take steroids either orally or intravenously. They may also receive disease-modifying therapy such as immunomodulators and biologic medications. Many patients do enjoy remission once they receive these powerful drugs; however, side effects can be difficult to tolerate. Patients who cannot tolerate these powerful drugs or do not achieve disease remission may have to take steroids every day. Chronic steroid use has many severe and sometimes permanent side effects. If these treatments fail, patients may need to have surgery to remove a portion of their intestines that have been damaged by Crohn’s disease.

In an effort to find safe and effective treatments for Crohn’s disease, researchers have been testing stem cells in laboratory animals. In one study, scientists used a chemical to cause colon inflammation (colitis) in mice. This chemical causes many of the symptoms of humans with Crohn’s disease experience such as diarrhea, tissue damage, and weight loss. The researchers then treated some of the mice with mesenchymal stem cells gathered from human fat tissue (adipose) to see if stem cells could improve the symptoms.

Remarkably, human stem cell treatment reduced diarrhea, inflammation, and disease severity in mice with colitis. The chemical colitis caused mice to lose approximately 15 to 20% of their body weight. Mice that received stem cell treatment regained most of the weight they had lost. Researchers also noted that mice treated with adipose-derived mesenchymal stem cells lived significantly longer than those that did not receive stem cell treatment.

Of course, this research was performed in laboratory animals, but it lays important groundwork for testing in humans. Indeed, since the publication of this report, researchers have been able to show that adipose-derived stem cells helped patients with Crohn’s disease. This exciting work will no doubt lead to future studies that may help pave the way to wider use of stem cells in the treatment of inflammatory bowel disease, such as Crohn’s disease.

Reference: Gonzalez, M. (2009). Adipose-Derived Mesenchymal Stem Cells Alleviate Experimental Colitis by Inhibiting Inflammatory and Autoimmune Responses. Gastroenterology. Volume 136, Issue 3, March 2009, Pages 978-989

Stem Cells Slow the Rate of Decline in Progressive Supranuclear Palsy

Stem Cells Slow the Rate of Decline in Progressive Supranuclear Palsy

Progressive supranuclear palsy, also known as PSP, is a disorder of the brain that gets worse over time (progressive neurodegenerative disorder). Many progressive supranuclear palsy symptoms are similar to Parkinson’s disease. These include rigidity, slowness of movement, cognitive (thinking) problems, difficulty speaking, and difficulty swallowing. While people with Parkinson’s disease can have an unsteady gait and “freeze,” these symptoms are much more prominent in people with progressive supranuclear palsy. Likewise, people with PSP have a particular eye problem called supranuclear gaze palsy, which causes PSP patients to have difficulty moving their eyes in certain directions.

Despite the similarities between PSP and Parkinson’s disease, there are no treatments for progressive supranuclear palsy as they are for Parkinson’s disease. Drugs like levodopa help reduce tremors and rigidity in people with Parkinson’s, but they have been largely ineffective in people with PSP. Some PSP patients may benefit from drugs like levodopa, but most experience severe visual hallucinations or other side effects, which causes them to stop the medication. Because there are so few treatments, patients with progressive supranuclear palsy rely on supportive care measures such as occupational and physical therapy, nutritional support, and palliative care.

To address this critical need, researchers are testing mesenchymal stem cells for their ability to treat progressive supranuclear palsy. Dr. Margherita Canesi and her colleagues selected five patients with progressive supranuclear palsy. Her research team used bone marrow from healthy volunteers to select healthy mesenchymal stem cells. The researchers then infused the mesenchymal stem cells into patients in a single infusion.

While patients with PSP normally deteriorate rapidly, the patients who received a single stem cell treatment remained stable for at least six months after treatment. Some patients still maintained function at the end of the study (12 months). All patients tolerated the treatment well, there were no major side effects. While the study was small, it suggests that stem cell treatment was able to change the natural course of the disease. Based on these encouraging results, the authors have set their sights on a randomized, placebo-controlled phase 2 study to further test mesenchymal stem cell treatments in patients with progressive supranuclear palsy. We look forward to their results with great enthusiasm.

 

 

Reference: Canesi, M. et al. (2016). Finding a new therapeutic approach for no-option Parkinsonisms: mesenchymal stromal cells for progressive supranuclear palsy. Journal of Translational Medicine. 14, Article number: 127 (2016).

How Exosomes Can Improve Stem Cell Therapy

How Exosomes Can Improve Stem Cell Therapy

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.

The Anti-Aging Properties of “Cell-Less” Mesenchymal Stem Cell Treatment

The Anti-Aging Properties of “Cell-Less” Mesenchymal Stem Cell Treatment

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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