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 Show Promise in the Treatment of Multiple Sclerosis

Umbilical Cord Mesenchymal Stem Cells Show Promise in the Treatment of Multiple Sclerosis

A new study has shown that a protocol for treating Multiple Sclerosis with stem cells is safe. According to the researchers, the potential for using stem cells in Multiple Sclerosis therapy warrants further investigation. The results of the study were published in the Journal of Translational Medicine.

Stem cells – and specifically, mesenchymal stem cells, have been increasingly used in the treatment of immune and inflammatory conditions. Based on the success that has been seen in these areas, scientists reasoned that mesenchymal stem cells may also represent a useful approach to treat Multiple Sclerosis, a neurological disease that involves the abnormal attack by the immune system on the myelin sheath that insulates nerves and allows nerve cells to communicate effectively and efficiently with one another.

To test this idea, the scientists used umbilical cord mesenchymal stem cells in 20 Multiple Sclerosis patients. The patients were given intravenous injections of the stem cells each day for seven days. The researchers evaluated the patients – with both neurological testing and nervous system imaging – at baseline, one month after treatment, and one year after treatment. The researchers found that the stem cell treatment improved neurological scores in patients and that lesions in the brain and cervical spinal cord were inactive one year after the stem cell injections. There were no serious adverse side effects associated with the treatment.

Based on these findings, it is possible that stem cells will provide a useful treatment option for those with Multiple Sclerosis. With more research, we will better understand exactly how stem cells can be used to help this population of patients.

 

Reference: Riordan, N.H. et al. (2018). Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis. Journal of Translational Medicine, 16(57), 1-12.

Mesenchymal Stem Cell Options for Erectile Dysfunction

Mesenchymal Stem Cell Options for Erectile Dysfunction

Erectile dysfunction is the most common sexual disorder among men. During an erection, blood enters the tissues within the penis and is temporarily trapped there. In erectile dysfunction, however, this process does not occur. A man who suffers from this condition is unable to achieve a penile erection sufficient for sexual intercourse.

Erectile dysfunction has many causes ranging from neurological conditions to vascular (blood vessel) conditions to psychological conditions. In most men, erectile dysfunction is caused by a problem in blood flow and nitric oxide production, which is why drugs like the Viagra and Cialis are effective for some men because they temporarily reverse these problems.

Results from a review of 54 research studies showed that stem cell-based therapies may be able to reverse these effects on a more permanent basis. For example, mesenchymal stem cells were able to increase the number of enzymes that produce nitric oxide. Likewise, mesenchymal stem cells increased the size of penile tissue in older rats. Indeed, stem cell injections were able to restore erectile function in rats with diabetes.

Based on these laboratory results, researchers have conducted clinical trials using stem cells to treat men with erectile dysfunction. In one such trial, researchers used a person’s own fatty tissue (adipose) to generate stem cells. They then injected those cells into men with erectile dysfunction. Eight out of 11 men treated with stem cells regained erectile function. In another small study, eight men with profound erectile dysfunction in whom oral ED treatments failed received placenta-derived stem cells. Two of the patients were able to achieve and sustain erections six weeks after treatment while an additional patient was able to do so after three months.

Laboratory studies of stem cells in the treatment of erectile dysfunction are extremely promising. The clinical studies in this area are limited, and the results are somewhat less impressive. Nonetheless, as improvements and refinements are made to stem cell technology, this approach could offer hope to men with erectile dysfunction, especially those men who have not been helped by ED drugs.

Reference: Albersen, M. et al. (2013). Stem-cell therapy for erectile dysfunction. Arab Journal of Urology. 2013 Sep; 11(3): 237–244.

 

Hyperbaric Oxygen Therapy Improves Cognition after Traumatic Brain Injury by Increasing Stem Cells

Hyperbaric Oxygen Therapy Improves Cognition after Traumatic Brain Injury by Increasing Stem Cells

Traumatic brain injury (TBI) encompasses a wide range of injuries, neurological problems, and outcomes. On one end of the spectrum is a concussion, which can be mild and short lasting. At the other end of the spectrum, traumatic brain injury can be lethal or leave patients with chronic mental and physical problems. Despite this range of severities, traumatic brain injury is one of the leading causes of disability in the United States, affecting over 13 million people. People who suffer from chronic symptoms related to traumatic brain injury may struggle with chronic seizures, memory problems, concentration problems, agitation, among others. TBI can have profoundly worsened a person’s quality of life and overall well-being.

Unfortunately, little can be done to treat traumatic brain injury directly. Aside from treating symptoms, the main treatment for TBI is to have the patient to rest and avoid stimulation in an effort to give the brain time to heal. Patients can regain some function through intensive work with physical, occupational, speech, and recreational therapist. However, the brain’s ability to heal itself is limited compared to other tissues of the body. In short, the brain has very little capacity to make new brain cells after we are born. So once TBI has occurred, patients either need to depend on other healthy areas of the brain or simply adapt to their circumstances.

Fortunately, researchers are finding ways to improve on nature through hyperbaric oxygen therapy. Drs. Shandley, Wolf and other hyperbaric medicine researchers recruited a group of 28 military veterans who sustained a traumatic brain injury in Iraq or Afghanistan. These individuals had ongoing cognitive problems as a result of their brain injuries. Researchers placed some study participants in 2.4 atm avoid hundred percent oxygen, while the others simply underwent a placebo experience at basically normal pressure and oxygen levels. The two groups underwent 30 exposures each and took a cognitive test before and after these treatments.

Hyperbaric oxygen therapy increased the number of stem cells in the blood of patients with TBI. In other words, hyperbaric oxygen treatment was able to move stem cells from the bone marrow and perhaps other tissues into the bloodstream. At the same time, those treated with hyperbaric oxygen performed better on tests of cognition including ImPACT, BrainCheckers, and PCL-M test. Moreover, no adverse effects of treatment were observed. Taken together, these results suggest 30 sessions of hyperbaric oxygen treatment at 2.4 atm was able to increase stem cells in the blood and improve cognition in US warfighters who suffered traumatic brain injury during combat. These results are encouraging news for the millions of veterans and nonveterans who sustained a traumatic brain injury every year.

 

Reference: Shandley, S. et al. (2017). Increased circulating stem cells and better cognitive performance in traumatic brain injury subjects following hyperbaric oxygen therapy. Undersea & Hyperbaric Medical Society. 2017 May-Jun;44(3):257-269.

 

Mesenchymal Stem Cells Exert Therapeutic Effects in Duchenne Muscular Dystrophy

Mesenchymal Stem Cells Exert Therapeutic Effects in Duchenne Muscular Dystrophy

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.

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