Stem Cells Restore Function of Regulatory T Cells from Multiple Sclerosis Patients

Stem Cells Restore Function of Regulatory T Cells from Multiple Sclerosis Patients

Scientists have long realized that multiple sclerosis is an inflammatory disease, and that the immune system, in a manner, attacks the brain and spinal cord. These inflammatory lesions cause patients to have severe neurological symptoms. Therefore, treatments for multiple sclerosis have focused on controlling the immune system.

There are current treatments of care for MS patients to manage their symptoms. They can help minimize the severity of the disease, but they may cause serious side effects. Consequently, researchers are constantly looker for newer, safer, less expensive alternatives.

While the precise cause of MS is still unknown, multiple sclerosis lesions contain high levels of an immune cell, specifically CD4+ T cells. These T cells become active in the central nervous system and interfere with the function of other T cells (regulatory T cells). Simply put, whatever causes MS creates abnormal regulatory T cells; healthy regulatory T cells are important for maintaining a balance between helpful and harmful immune system functions.

In the scientific research journal Oncotarget, Yang and co-authors showed experimentally for the first time that umbilical cord-derived mesenchymal stem cells could repair defective regulatory T cells in patients with MS.

The scientists collected mesenchymal stem cells from umbilical cord tissue (the tissue that is usually thrown away as medical waste after live birth). They also collected peripheral blood mononuclear cells (i.e. T cells, B cells, natural killer cells, and monocytes) from patients with MS and healthy volunteers. Stem cells and peripheral blood mononuclear cells were combined in the lab for 3 days. After incubation, samples with stem cells had a higher proportion of regulatory T cells, and those regulatory T cells had greatly improved their function. In fact, stem cell treatment made the defective regulatory T cells function much like regulatory T cells from healthy volunteers.

More work must be done to take this technology from the lab and into the clinic, but the proof of concept is remarkable. Stem cell treatment has been shown to be safe in scores of clinical trials. Thus, if umbilical cord-derived mesenchymal stem cells can improve regulatory T cell function in patients with MS, the impact could be beneficial to help improve multiple sclerosis symptoms.

Reference: Yang, H., et al. (2016). Umbilical cord-derived mesenchymal stem cells reversed the suppressive deficiency of T regulatory cells from peripheral blood of patients with multiple sclerosis in a co-culture – a preliminary study. Oncotarget 2016; 7:72537-72545.

Using Stem Cells to Treat Nerve Damage in Multiple Sclerosis

Using Stem Cells to Treat Nerve Damage in Multiple Sclerosis

Multiple sclerosis is an inflammatory disease of the brain and spinal cord.  The immune system mistakenly attacks the covering of nerve axons called the myelin sheath. Just as an electrical cord that has lost its insulation cannot work properly, so too is it with nerve cells that have been destroyed by MS. Unfortunately, when electrical signals (action potentials) cannot move through axons, it causes neurological problems and disability. People with MS may lose the sense of touch, the sense of sight, the ability to move or walk, and the ability to control bowel or bladder function.

While treatments for MS are intended to reduce inflammation, no treatment has been developed that can repair damaged nerve cells. Scientists recently reviewed the status of stem cell clinical trials to treat multiple sclerosis. The results are encouraging.

No fewer than 8 clinical trials have shown that mesenchymal stem cells can be safely used in patients with MS. Moreover, the phase 2 clinical trials within this group showed that various stem cell treatments reduced the severity of MS. This is especially important because mesenchymal stem cells actually reduced the number of lesions (areas of inflammation and injury) in patients with MS compared to placebo.

Importantly the review determined stem cells were able to improve MS disease and nerve destruction regardless of whether the stem cells were collected from fat tissue, umbilical cord, or bone marrow. Stem cells retrieved from fat (i.e. adipose) reduced MS relapses and delayed the progression of the disease. Likewise, fat-derived stem cells improved sexual satisfaction and improved bowel control 12 months after treatment.

Why are the results of fat-derived stem cells so exciting? Because bone marrow can be difficult to access and umbilical cord tissue must be collected from donors. On the other hand, virtually everyone has excess fat on their bodies. This fat can be safely and easily removed with a simple extraction such as liposuction. A patient’s own fat cells can be removed, processed, and re-infused as stem cell treatment. When someone uses their own stem cells, there is no risk that the body will reject the infusion (as could theoretically happen to donor stem cells).

These results are exciting and welcome information for those who suffer from multiple sclerosis. As larger clinical trials are performed and previous results are replicated, we may see an increase in stem cell treatment options to help manage the symptoms of multiple sclerosis.

Reference: Bejargafshe, M., et al. (2019). Safety and efficacy of stem cell therapy for treatment of neural damage in patients with multiple sclerosis. Stem Cell Investigation. 2019; 6:44.

Mesenchymal Stem Cells and Neurodegenerative Diseases

Mesenchymal Stem Cells and Neurodegenerative Diseases

As the name suggests, neurodegenerative diseases are a disease of the nervous system in which nerve cells (i.e. neurons) become dysfunctional and die. As more nerve cells die, certain brain functions slow, change or stop. Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and Amyotrophic lateral sclerosis (ALS) are examples of debilitating and even fatal neurodegenerative diseases. There are no cures for these diseases, but symptom management is the primary focus for patients seeking treatment options.

Neurodegenerative diseases are an attractive target for regenerative medicine. The approach makes sense intuitively; if brain cells are inflamed, dysfunctional, and dying, can mesenchymal stem cells be applied as a targeted approach so that they may differentiate into new brain cells and release all the helpful substances stem cells are known to release. Many researchers share this optimism and believe in the promise of stem cells as a treatment for neurodegenerative diseases. Indeed, Drs. Joyce and coauthors discuss what steps have already been taken to develop stem cells into a potential treatment for neurodegenerative diseases.

The authors describe scientific studies that show how mesenchymal stem cells “promote endogenous neuronal growth, decrease apoptosis and regulate inflammation.” In other words, stem cell transplantation supports nerve cell growth, decreases cell death, and reduces the damaging inflammation that is seen in some neurodegenerative diseases like multiple sclerosis.

According to the scientists, stem cells “can mediate modification of the damaged tissue microenvironment to enhance endogenous neural regeneration and protection.” This means that stem cells can make the area around the diseased brain more favorable to nerve cell growth and development. Stem cells create a protective environment for nerve cells to live and operate.

Clinical trials that study the effects of stem cells in neurodegenerative diseases are progressing. Some studies show that stem cells might be able to slow the rate at which muscle strength declines and are considered safe for those with ALS. Likewise, patients with Huntington’s disease showed motor and cognitive improvements two years after receiving a stem cell transplant into the damaged region of their brains. Moreover, stem cells transplanted into patients with Parkinson’s disease were found to be alive and well 10 years after transplantation. Perhaps more importantly for patients, stem cells provided relief of Parkinson’s disease symptoms.

As of now, stem cell treatments for neurodegenerative diseases can be directed to the targeted tissues with administration techniques such as intranasal or intrathecal injections to bypass the blood-brain barrier. While these injections have been shown time and again to be safe, patients and their providers must consider the process and their safety. Continued research is ongoing and those seeking an alternative option should do their research and discover how regenerative medicine may potentially help them manage their symptoms.

Reference: Joyce, N., et al. (2010). Mesenchymal stem cells for the treatment of neurodegenerative disease. Regenerative Medicine. 2010. Nov; 5(6): 933-946.

Mesenchymal Stem Cells Can Modulate the Immune System

Mesenchymal Stem Cells Can Modulate the Immune System

The human immune system can be one of our biggest assets or one of our greatest foes. The immune system protects us against foreign invaders like viruses and bacteria. It is essential for helping us maintain immunity over a lifetime, whether from immunizations or previous infections. We could not live without our immune systems.

On the other hand, the human immune system is the cause of numerous diseases. Autoimmune diseases like multiple sclerosis, ulcerative colitis, systemic lupus erythematosus, and Crohn’s disease are caused by an immune system that mistakenly attacks our own tissue. Organ and bone marrow transplants fail because the body’s immune system rejects the transplant. When the immune system is functioning normally, it is life-sustaining; however, when the immune system falters, it can cause serious disease, suffering, and even death.

Compared to other diseases, the treatments for autoimmune diseases and other diseases that involve the immune system are limited. Doctors can prescribe steroids to knock down the immune response. These powerful drugs can control disease flareups, but they aren’t a cure. Moreover, steroids cause terrible side effects when taken long-term.

While there have been some recent developments in the treatment of certain autoimmune diseases (e.g. disease-modifying drugs for inflammatory bowel disease), medications are still limited. That is why scientists are actively studying the immune-modulating power of mesenchymal stem cells.

Mesenchymal stem cells exert a number of beneficial effects on the cells of the immune system. Mesenchymal stem cells can suppress T-cells, B-cells, dendritic cells, and natural killer cells (cells that participate in autoimmune diseases). Likewise, mesenchymal stem cells induce and affect the action of regulatory T-cells. This can help fine-tune the immune system, potentially shifting the balance from harmful to helpful immune system function.

Mesenchymal stem cells have been shown to be effective in various Phase I and Phase II clinical trials to treat multiple sclerosis, Crohn’s disease, lupus, ulcerative colitis, and even diabetes. While the clinical trials are often small—15-40 patients—the effects are impressive. Furthermore, treatment with mesenchymal stem cells is consistently safe; in study after study, the risk of serious adverse events is vanishingly small.

As with most fields of medicine, these clinical trials will need to be replicated in larger, Phase III trials. That being said, some large trials have already been conducted with favorable results. Perhaps the best example of a large trial testing the effect of mesenchymal stem cells on immune system function is in the field of transplantation medicine. The prestigious Journal of the American Medical Association (JAMA) published a clinical trial of 159 patients undergoing kidney transplants. Stem cell treatment reduced the incidence of kidney rejection, decreased the risk of opportunistic infection, and was associated with better kidney function 1 year after treatment.

The results from dozens of clinical trials suggest mesenchymal stem cells are powerful modulators of immune cell function and have the potential to one day be tools to treat diseases caused by the immune system. We anxiously await further results from large, Phase III trials.

Reference: Gao, F., et al. (2016). Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death & Disease. 2016, Jan; 7(1): e2062.

Mesenchymal Stem Cell Treatment for Multiple Sclerosis

Mesenchymal Stem Cell Treatment for Multiple Sclerosis

Multiple sclerosis is a chronic neurological disease that affects the brain and spinal cord. In multiple sclerosis, an immune reaction breaks down the covering around neuronal axons, myelin. Depending on where in the brain or spinal cord this inflammation occurs, patients with multiple sclerosis may experience weakness, a lack of sensation, double vision, difficulty walking, difficulty with balance, problems with urination, dizziness, and/or pain. Over time, patients with multiple sclerosis require assistive devices such as canes or wheelchairs to get around, and some ultimately become bedridden.

Multiple sclerosis can be divided into 4 types:

Clinically isolated syndrome – The first episode of MS; about two-thirds of people with a clinically isolated syndrome of MS will go on to have one of the other types listed below

Relapsing-remitting – Patients have symptoms for a time, which resolve, but then eventually return

Secondary progressive – After some cycles of flare-ups and remissions, the disease is present all the time; some patients with relapsing-remitting disease develop secondary progressive MS

Primary progressive – Once symptoms start, they do not resolve but instead get progressively worse

Fortunately, there are some treatments that can change the course of multiple sclerosis. There are several disease-modifying agents available for people with relapsing-remitting disease and a few for progressive multiple sclerosis. These drugs can reduce the rate at which symptoms get worse or extend the length of time between flare-ups. Unfortunately, not everyone can tolerate these drugs, and, in others, the drugs are not very effective. None of these drugs is a cure for multiple sclerosis.

Researchers have turned to mesenchymal stem cells as a possible treatment for multiple sclerosis. These cells have the ability to regulate the immune system and support the nervous system. There have been so many clinical trials of stem cells in multiple sclerosis that researchers can now perform a meta-analysis on them. A meta-analysis is a special study in which all trials on a particular topic are combined and analyzed, i.e., a study of studies.

In their recent meta-analysis, Dr. Zhou and co-authors identified 9 clinical studies using mesenchymal stem cells to treat multiple sclerosis. They found that the rate of disease progression with stem cell treatment was 16% at 6 months and 35% at 1 year. This is a faster rate of decline than disease-modifying treatment, but better than no treatment at all. Importantly, the MS patients treated with stem cells had much more severe disease than average—it was a group for whom disease-modifying treatment had failed. From this perspective, stem cell treatment for MS was a great success.

Most patients had no evidence of disease activity at 6 months (72%) and 1 year (62%) after autologous mesenchymal stem cell treatment. This a substantial duration of time to be disease-free.

The authors noted that stem cells transplanted via the intrathecal route (i.e. directly in the cerebrospinal fluid) resulted in a slower progression of disability.

Taken together, these results are encouraging. The authors also concluded that mesenchymal stem cell treatment was safe. More work with larger patient groups are needed, but this is an exciting avenue of research.

Reference: Zhou, Y., et al. (2019). Autologous Mesenchymal Stem Cell Transplantation in Multiple Sclerosis: A Meta-Analysis. Stem Cells International. 2019, Volume 2019 |Article ID 8536785.

Stem Cell Therapy for Crohn’s – How it May Help Perianal Fistulas

Stem Cell Therapy for Crohn’s – How it May Help Perianal Fistulas

A recent study has shown how stem cells may be able to help Crohn’s disease patients who suffer from perianal fistulas. The researchers specifically investigated how stem cell therapy for Crohn’s Disease compared to conventional approaches including antibiotics and immunosuppressors. Because research is still in its infancy, there has been great interest in how to best address perianal fistulas in Crohn’s disease patients.

For their study, the scientists studied adults between the ages of 19 and 68. The patients were divided into three groups: one group received mesenchymal stem cell therapy applied locally, another received a combination of cellular and anti-cytokine therapy, and a third received a combination of immunosuppressors and antibiotics. The researchers looked at the impact of these three therapeutic interventions on the frequency of relapses of perianal fistulas and evaluated patients with the index of perianal activity of Crohn’s disease (PCDAI).

Their results showed that the combined cellular and anti-cytokine therapy improved perianal lesions in Crohn’s disease patients more so than did the immunosuppressor and antibiotic combination. Specifically, with the stem cell and anti-cytokine approach, fistulas remained closed longer and fistulas recurred less frequently. Future research should help to determine if and how this stem cell approach can provide an effective and safe long-term therapy for Crohn’s disease patients with perianal fistulas.

Reference: Knyazev, OV et al. (2018). Stem cell therapy for perianal Crohn’s disease. Ter Arkh, 90(3), 60-66.

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