Traumatic spinal cord injury is a potentially devastating event in which the nerves and nerves cells in the spinal cord are damaged. In the United States, more than a quarter of a million people struggle with the lifelong consequences of traumatic spinal cord injury. The consequences of spinal cord injury vary from person to person, but each person usually must deal with several complications. Many people with spinal cord injury are paralyzed. They are at risk for pressure ulcers, blood clots in the legs, urine and bowel problems, and sexual dysfunction. Despite being paralyzed, as many as two-thirds of patients with spinal cord injury experience chronic pain, which is difficult to treat. Spinal cord injury can also affect how the heart and lungs function.
There are no specific treatments for spinal cord injury. If the injury is treated early, steroids and spine surgery/neurosurgery can help reduce long-term complications. In some cases of incomplete spinal cord injury, physical therapy can help people regain some degree of function. For the most part, treatment is aimed at reducing symptoms rather than curing the injury. Treating the symptoms helps make the disease less of a burden, but is by no means the same as a cure.
Because spinal cord injury has such long-lasting and devastating effects, researchers are actively pursuing ways to heal injured spinal cord nerve cells. One possible way to do this is through the use of stem cells.
Liu and coauthors conducted a clinical trial on 22 patients with spinal cord injury. The doctors collected mesenchymal stem cells from umbilical cord tissue that would normally be discarded as medical waste after delivery. They purified the stem cells and then used them to treat the injured patients. Astoundingly, stem cell treatment was effective in 13 of 22 patients. Patients who achieved benefit from stem cells enjoyed the return of motor function, sensory function, or both. All patients who were treated with stem cells reported less pain, improved sensation, better movement, and a greater ability to provide self-care. Importantly, the treatment did not cause any notable side effects for up to three years after treatment.
These clinical trial results are truly remarkable, but it is important to note that the number of patients treated was small and further testing is needed. Nevertheless, the researchers concluded that treatment with mesenchymal stem cells derived from umbilical cells is safe, and can improve function and quality of life in most patients with spinal cord injury.
Reference: Liu et al. (2013). Clinical analysis of the treatment of spinal cord injury with umbilical cord mesenchymal stem cells. Cytotherapy. 2013 Feb;15(2):185-91.
Of all conditions that affect the central nervous system, Multiple Sclerosis (MS) is the most common in young adults. The severity of multiple sclerosis varies considerably and can affect almost every organ system in the body affecting eyesight, bowel function, bladder function, and sexual function. Multiple sclerosis may cause cognitive problems, depression, seizures, fatigue, and pain. Most people with multiple sclerosis will have a relapsing-remitting course, which means they will have periods of relative health punctuated by flare-ups of the condition. About one out of ten people with the condition will have primary progressive multiple sclerosis, which means once the disease occurs it almost constantly causes symptoms and progresses over time.
Multiple sclerosis appears to be an inflammatory condition that affects the covering around nerves. During acute flareups/exacerbations, physicians usually prescribe a powerful steroid medication such as methylprednisolone to combat the inflammation. Patients with multiple sclerosis generally always require some sort of treatment to help manage their immune system. No fewer than 15 immune modulating treatments have been used to treat multiple sclerosis, none of which provides a cure. As such, researchers are seeking new and innovative ways to treat this potentially debilitating condition.
Researchers at the Tisch Multiple Sclerosis Research Center of New York chose to focus their research efforts on a particular type of stem cell, namely bone marrow-derived mesenchymal stromal cells. The researchers harvested these cells from the patients themselves (autologous stem cells). Then, in their laboratory, scientists used various means to prompt the cells to become neural progenitors. A neural progenitor cell is a cell that can become any of the three main types of brain cells: neurons, astrocytes, or oligodendrocytes. Incidentally, oligodendrocytes are believed to be most affected in multiple sclerosis.
Harris and co-authors at the Tisch Center enrolled six patients with progressive multiple sclerosis. These six patients had failed to find relief from other conventional multiple sclerosis treatments. The researchers provided between 2 to 5 infusions of neural progenitor cells into the spinal fluid. The multiple sclerosis patients treated with the cells tolerated the treatment very well. No serious adverse events occurred, nor were there any safety concerns during treatment. Impressively, four of the six patients—for whom no other multiple sclerosis treatment worked—had a measurable clinical improvement after stem cell treatment.
Based on the results of this clinical study, the scientists concluded that neural progenitor cells created from autologous mesenchymal stromal cells were safe to use in patients with primary progressive multiple sclerosis. Moreover, the beneficial effect witnessed in two-thirds of treated patients suggests that these cells may be able to help patients with even the most severe and difficult-to-treat forms of multiple sclerosis. Of course, additional testing is required before this treatment becomes commonplace, but the results of this first-in-human clinical study are extremely encouraging.
Reference: Harris et al. (2016). Clinical safety of intrathecal administration of mesenchymal stromal cell-derived neural progenitors in multiple sclerosis. Cytotherapy. 2016 Dec;18(12):1476-1482.
Spinal cord injury is severe neurological condition in which
the major mode of transmission between the brain and the body is disrupted.
When higher levels of the spinal cord are injured, for example, in the neck,
the injury can be immediately fatal. Those who survived spinal cord injury are
often left paralyzed and at risk for a number of comorbid conditions
such as pneumonia, depression, skin ulceration infection, urinary tract
infections, and pain.
If patients who sustain spinal cord injury can receive
medical treatment quickly, physicians may administer glucocorticoids to help
reduce swelling around the injury and preserve spinal cord function. Patients
may also undergo therapeutic
hypothermia (a.k.a. targeted temperature management, whole body cooling),
also to help reduce inflammation and prevent scar tissue from forming around
the damaged spinal cord.
After the first few days to weeks after spinal cord injury,
not much can be done to change the outcome of the disease. Patients may undergo
intensive physical, occupational, and speech therapy to help regain function,
but more often than not the neurological deficits are mostly permanent. Hence,
researchers are feverishly searching for ways to treat spinal cord injury and,
by extension, prevent or reduce paralysis and other chronic complications.
Mesenchymal stem cells are an intriguing potential therapy
for spinal cord injury. These cells can easily be obtained from many different
tissues including bone marrow and fat among others. In animals, mesenchymal stem
cells have been shown to improve changes that occur during spinal cord injury,
namely the regeneration
and strengthening of nerve cells in the spinal cord. Research
has also shown how adipose-derived stem cells are a potential option for those
with neurological conditions such as spinal cord injury.
To test this possible effect in humans, researchers collected
mesenchymal stromal (stem) cells from patients with spinal cord injury in
their upper back (i.e. thoracic spinal cord). Researchers then prepared and administered
those cells back into the cerebrospinal fluid of the same patients. Each
patient received two or three injections of approximately 1,000,000 cells per
kilogram body weight. There were no adverse effects of the treatment for up to
two years after injection. MRI imaging showed no abnormalities resulting from
stem cell infusion. While the authors write that there were too few patients to
make any firm conclusions about the efficacy of the treatment, they were
strongly encouraged by the safety of the procedure. In fact, they use these
results to begin a placebo-controlled clinical trial.
Satti et al. (2016). Autologous mesenchymal stromal cell
transplantation for spinal cord injury: A Phase I pilot study. International Society for Cellular Therapy,
Most organs of the body recover from injury by generating new, healthy cells. Not every organ of the body has the same ability to form new cells, however. The skin is an example of an organ that has an amazing ability to regenerate. Liver and lung also have the ability to form new cells, but not as dramatically as skin. Kidney and heart have even less ability to repair and regenerate. On the opposite end of the spectrum from the skin is the brain, which has very little capacity to regenerate once it has been damaged or destroyed. All of these organ systems, especially those that are relatively unable to repair themselves, could theoretically benefit from stem cells.
Mesenchymal stem cells, also known as stromal cells, are multipotent stem cells derived from bone marrow, umbilical cord, placenta, or adipose (fat) tissue. These cells can become the cells that make up bone, cartilage, fat, heart, blood vessels, and even brain. Mesenchymal stem cells have shown a remarkable ability to help the body to produce new cells. Researchers are now realizing that the substances stem cells release may be more important than any new cells they may become. In other words, stem cells can directly become new healthy cells to a certain degree, but they can also release substances that dramatically increase the number of new, healthy cells.
Mesenchymal stromal stem cells release small packets called exosomes. These exosomes are filled with various substances that promote cell and tissue growth. Some of the most interesting and potentially useful substances are cytokines and micro RNA. Cytokines are the traffic cops of cellular repair, signaling certain events to take place while stopping others. Having the right cytokines in a particular area is critical for new tissue growth. The micro RNA released by stem cell exosomes is potentially even more exciting than cytokines. These tiny bits of RNA can directly affect how healthy and diseased cells behave. Micro RNA has a powerful ability to control the biological machinery inside of cells.
Exosomes exhibit a wide array of biological effects that promote the repair and growth of damaged and diseased organs. They promote the growth of skin cells and help wounds heal. Exosomes can reduce lung swelling and inflammation and even help the lung tissue heal itself (i.e. reduced pulmonary hypertension, decrease ventricular hypertrophy, and improve lung vascular remodeling). These small packets released by stem cells help prevent liver cells from dying (i.e. prevents apoptosis), promote liver cell regeneration, and slow down liver cirrhosis (i.e. fibrosis). Exosomes can also help protect the kidneys during acute injury and reduce the damage that occurs during a heart attack.
Several clinical trials are underway designed to allow these exciting developments to be used to treat patients. As the researchers state, “Extensive research and clinical trials are currently underway for the use of MSCs as regenerative agents in many diseases including spinal cord injury, multiple sclerosis, Alzheimer’s disease, liver cirrhosis and hepatitis, osteoarthritis, myocardial infarction, kidney disease, inflammatory bowel disease, diabetes mellitus, knee cartilage injuries, organ transplantation, and graft-versus-host disease.” We can reasonably expect that exosomes will be used to treat at least some of these conditions in the very near future.
Reference: Rani al. (2015). Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications. Molecular Therapy. 2015 May; 23(5): 812–823.
Tissue injury is common to many human diseases. Cirrhosis results in damaged, fibrotic liver tissue. Idiopathic pulmonary fibrosis and related lung diseases cause damage to lung tissue. A heart attack damages heart tissue, just as a stroke damages brain tissue. In some cases, such as minor tissue injury, the damaged tissue can repair itself. Over time, however, tissue damage becomes too great and the organ itself can fail. For example, long-standing cirrhosis can cause liver failure.
One area of active research is to find ways to protect tissue from injury or, if an injury occurs, to help the tissue repair itself before the damage becomes permanent and irreversible. Indeed, tissue repair is one of the main focuses of regenerative medicine. Likewise, one of the most promising approaches in the field of regenerative medicine is stem cell therapy. Researchers are learning that when it comes to protecting against tissue injury and promoting tissue repair, exosomes harvested from stem cells are perhaps the most attractive potential therapeutic.
Why are stem cell exosomes so promising? Exosomes are small packets of molecules that stem cells release to help the cells around them grow and flourish. While one could inject stem cells as a treatment for diseases (and they certainly do work for that purpose) it may be more effective in some cases to inject exosomes directly. So instead of relying on the stem cells to produce exosomes once they are injected into the body, stem cells can create substantial amounts of exosomes in the laboratory. Exosomes with desired properties could be concentrated and safely injected in large quantities, resulting in a potentially more potent treatment for the disease.
Indeed, researchers have shown that extracellular vesicles (exosomes and their cousins, microvesicles) can be collected from stem cells and used to treat a variety of tissue injuries in laboratory animals.
Just a few examples of this research:
- Exosomes from umbilical cord-derived mesenchymal stem cells were able to accelerate skin damage repair in rats who had suffered skin burns.
- Exosomes from the same type of stem cell protected the lungs and reduced lung blood pressure in mice with pulmonary hypertension.
- Exosomes from endothelial progenitor cells protected the kidney from damage caused by a lack of blood flow to the organ.
In this growing field of Regenerative Medicine, research is constant and building as new science evolves from stem cell studies. Researchers are closing in on the specific exosomes that may be helpful in treating human diseases caused by tissue injury.
Reference: Zhang et al. (2016). Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles. International Journal of Molecular Sciences. 2016 Feb; 17(2): 174.
Heart disease is the leading cause of death in the United States, killing over half a million people every year. Heart disease encompasses several conditions and diseases, but the most common causes of deadly heart disease are a heart attack, heart rhythm problems, and heart valve problems. In each of these cases, damaged heart tissue becomes dysfunctional and the heart cannot pump blood efficiently or effectively. To combat this deadly set of diseases, researchers are searching for ways to heal and regenerate heart tissue. Stem cells and stem cell exosomes have shown promise.
While stem cells have been used in a variety of conditions, researchers long doubted the benefit of stem cells in heart disease. The heart, it was believed, was not a “hormonal” organ and thought to be relatively unresponsive to things like cytokines and other messengers. Fortunately, new research has completely changed this viewpoint. According to Drs. Sean Davidson, Kaloyan Takov, and Derek Yellon of the Hatter Cardiovascular Institute in the United Kingdom, “Most, if not all, cells of the cardiovascular system secrete small, lipid bilayer vesicles called exosomes.” The scientists go on to say that exosomes from stem cells “have been shown to be powerfully cardioprotective” and that exosomes produced by stem cells are capable of “activating cardioprotective pathways.”
In simpler terms, the heart and blood vessels are sensitive to the beneficial effects of exosomes. Thus, if exosomes are collected from stem cells, purified and concentrated, and then reinjected into the body, they can repair heart tissue. For example, exosomes collected from mesenchymal stem cells were able to reduce the amount of damage caused by a heart attack in mouse, and improve heart recovery after the event. This could have profound implications for humans who suffer a heart attack since damaged heart tissue can lead to heart failure, heart valve problems, and heart rhythm problems.
The study of stem cells and stem cell exosomes in heart disease is a relatively new science. Clinical trials will need to be performed to determine the role of exosomes in the treatment of heart disease. However, these findings represent an exciting avenue of research in the field of cardiology and regenerative medicine.