Mesenchymal Stromal Cells are Safe and Well-Tolerated in ALS

Mesenchymal Stromal Cells are Safe and Well-Tolerated in ALS

Amyotrophic lateral sclerosis (ALS) is an incurable neurologic disorder that causes muscle weakness, and disability. In ALS, nerve cells degenerate causing muscle weakness and atrophy. ALS affects the nerve cells that connect the brain to the spinal cord (upper motor neurons), and nerve cells that connect the spinal cord to muscles (lower motor neurons). While some patients with ALS will experience paresthesias (numbness and tingling), most nerves that detect sensations remain intact until the very latest stages of the disease. Over time, people with ALS may experience cognitive problems such as mild dementia, though most stay mentally sharp. Patients with ALS may also experience Parkinson’s-like symptoms, such as tremor and slowness of movement (bradykinesia). When the nerves that control swallowing or breathing become dysfunctional, ALS can become life-threatening or lethal. Damage to these nerves and muscles could lead to aspiration pneumonia, and respiratory failure, respectively.

ALS is also known as Lou Gehrig’s disease because the famed New York Yankee publicly struggled with ALS. Perhaps people alive today are more familiar with another patient who suffered from ALS, the Nobel laureate physicist, Stephen Hawking. Dr. Hawking was well known for being confined to a wheelchair and almost completely paralyzed, requiring a specialized computer interface to communicate.

There is no specific treatment for ALS. Therapy is aimed at controlling the symptoms of the disease. For example, patients may have a breathing tube placed in their neck (tracheostomy) and be connected to a ventilator to help support breathing. Likewise, a feeding tube in the stomach can help patients receive hydration and nutrition if they cannot safely swallow food because of neck muscle weakness. Physical therapists help patients maximize the strength and function. Certain medicines can be used to help treat muscle spasms, sleep problems, pain, and depression.

Since there is no cure for ALS, and really no specific treatment for the condition, there is considerable interest in discovering effective treatments. One of the most promising potential therapies is to use stem cells to treat ALS. Since ALS is caused by the destruction and loss of motor neurons, a reasonable treatment approach is to use stem cells that can become motor neurons and promote motor neuron growth and development.

Recently, researchers conducted two clinical trials to evaluate the safety and feasibility of using bone marrow-derived mesenchymal stromal cells to treat patients with ALS. In one clinical trial, the researchers infused stem cells intravenously, while in the other they infused the stem cells into the cerebrospinal fluid around the spine (intrathecally). Patients in both trials were followed for up to 12 months after the infusion to see if the stem cells caused side effects. During the follow-up period, there were no reports of adverse events related to the treatment. Given the success of these trials, this work clears the way for future clinical trials to study the efficacy of stem cells for treating amyotrophic lateral sclerosis.

Reference: Nabavi et al. (2019). Safety, Feasibility of Intravenous and Intrathecal Injection of Autologous Bone Marrow-Derived Mesenchymal Stromal Cells in Patients with Amyotrophic Lateral Sclerosis: An Open-Label Phase I Clinical Trial. Cell Journal. 2019 Jan;20(4):592-598.

Stem Cells Show Promise for Helping Alzheimer’s Disease with Neurodegenerative Disease via Multiple Mechanisms

Stem Cells Show Promise for Helping Alzheimer’s Disease with Neurodegenerative Disease via Multiple Mechanisms

Alzheimer’s disease is the most common form of dementia, and though its prevalence is growing, there are currently no medical interventions that are able to reverse or slow the disease. Most current therapies address the symptoms of Alzheimer’s disease rather than the underlying cause of the disease.

Stem cells appear to offer a promising opportunity for treating Alzheimer’s disease and other neurodegenerative disorders, and a recent review published in Current Alzheimer Research has covered research into the ways stem cells can be applied to these disorders. Specifically, the authors of the review discuss the stem cell sources that may offer the potential to treat neurodegenerative diseases and the mechanisms by which these stem cells may confer benefits to this set of patients.

According to data collected so far, stem cells may be both safe and effective in treating neurodegenerative disorders like Alzheimer’s disease, but the mechanism by which they produce benefits for those with these disorders is not entirely clear. There are some data that show that the replacement of degenerated tissue with new proliferative stem cells accounts for stem cell benefits in models of neurodegenerative disorders, while other data show that stem cells can lead to advantageous enhancements in the expression of synaptic proteins.

Evidence from other studies, however, suggest that stem cells help with neurodegenerative disease through the release of neurotrophic factors that lead to paracrine benefits. Additional studies point to modulation of the immune system as the way that stem cells may help those with neurodegenerative disorders.

Future research will help to elucidate the specific mechanisms by which stem cells can provide effective therapy for people with neurodegenerative disorders. It may be the case that a variety of stem cell types used in multiple ways can be helpful for neurodegenerative disease therapy, and research will help to delineate the different ways stem cells can be used and inform the therapies that are developed.

 

Reference: Bali, P, et al. (2017). Potential for stem cells therapy in Alzheimer’s disease: Do neurotrophic factors play a critical role? Current Alzheimer Research, 14(2), 208-220.

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.

Stem Cells Showing Promise for Intervertebral Disc Regeneration and Reduction of Back Pain

Stem Cells Showing Promise for Intervertebral Disc Regeneration and Reduction of Back Pain

Chronic low back pain is a common condition that can significantly reduce the quality of life. The degeneration of the intervertebral disc is one cause for low back pain, and there is no therapeutic intervention that effectively reverses this type of degeneration. Both non-surgical and surgical treatments that are currently used for chronic low back pain aim to help the symptoms associated with the condition but do not address the underlying cause. Recently, however, researchers have begun to explore the ways in which stem cells may be used to help regenerate the intervertebral disc to restore functioning and eliminate low back pain over the long-term. A review of the relevant literature was recently published in Translational Pediatrics.

The intervertebral disc does not have a large potential to regenerate itself, so it is a challenge to find the best cell sources to facilitate such regeneration. Adult mesenchymal stem cells, which are found most often in bone marrow and also in fat, or adipose, tissue are attractive candidates for this type of regeneration given their high capacity to proliferate and to differentiate into different types of cells. In addition, they can self-renew, are highly accessible, and unlike some other types of stem cells, there are no ethical issues associated with their retrieval.

Given the success of mesenchymal stem cell transplantation in preclinical studies of intervertebral disc degeneration, the use of these cells has progressed to clinical trials. Autologous bone marrow mesenchymal stem cells – meaning stem cells taken from the bone marrow of the patients themselves – have been reported in the treatment of disc degeneration in patients with leg and back pain. Reduced pain has been observed at one and two years after transplantation. Importantly, the clinical trials investigating the use of stem cells in intervertebral disc regeneration have provided evidence that the relevant procedures are not only effective but also clinically safe. Future research will help to clarify if and how these and other types of stem cells may be used to reverse intervertebral disc regeneration and the associated chronic low back pain.

 

Reference: Wei, A. et al. (2014). Mesenchymal stem cells: potential application in intervertebral disc regeneration. Translational Pediatrics, 3(2), 71-90.

Umbilical Cord Derived Mesenchymal Stem Cells Restore Function After Stroke

Umbilical Cord Derived Mesenchymal Stem Cells Restore Function After Stroke

An ischemic stroke is a devastating event. An ischemic stroke is caused when a blood clot blocks blood flow to a portion of the brain. If the blood cannot deliver oxygen and nutrients, brain cells in the affected area die. Whatever functions that area of the brain once performed are now lost—brain cells do not regenerate the same way as other cells do.

Not surprisingly, researchers are trying to find ways to restore dead brain cells so that patients can regain function. Stem cells are one of the most promising options in this pursuit. Stem cells can reduce brain damage caused by ischemia (lack of blood flow, nutrients, and oxygen). Moreover, stem cells can help animals with stroke regain neurological function.

Scientists have wondered, however, whether mesenchymal stem cells taken from the umbilical cord can achieve the same effects. Umbilical cord tissue is plentiful and the cells taken from the umbilical cord have many incredible properties.

Dr. Zhang and researchers in his group extracted mesenchymal stem cells from umbilical cord tissue collected from humans. This umbilical cord tissue is usually thrown away after a baby is born, but researchers have been collecting this material because it is rich in mesenchymal stem cells. The researchers then created ischemic strokes in rats by blocking one of the arteries to the brain. They then used stem cells to try to block the damaging effect of stroke in these rats.

The stem cells were given to the rats intravenously. The stem cells moved from the bloodstream into the brain and collected in the area of the stroke. Some of the stem cells actually became new brain cells in the damaged area. Moreover, rats treated with stem cells had better physical functioning than animals who did not receive stem cell treatment.

While this study was performed in rats, the implications for humans are profound. This work shows that mesenchymal stem cells taken from the umbilical cord are capable of improving function after stroke. This is exited news since it is much easier to obtain stem cells from umbilical cord tissue that it is from bone marrow (which requires an invasive procedure).

 

Reference: Zhang, Lei et al. (2017). Neural differentiation of human Wharton’s jelly-derived mesenchymal stem cells improves the recovery of neurological function after transplantation in ischemic stroke rats. Neural Regeneration Research. 2017 Jul; 12(7): 1103–1110.

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