Using Stem Cells to Rebuild the Heart after a Heart Attack: Clinical Trial Results

Using Stem Cells to Rebuild the Heart after a Heart Attack: Clinical Trial Results

A myocardial infarction, commonly known as a heart attack, occurs when blood flow through the coronary arteries is blocked. A heart attack usually happens to people with atherosclerotic coronary heart disease, which narrows one or more of the coronary arteries. A blood clot becomes lodged in the narrowed artery, preventing blood from reaching the heart muscle. Because the heart needs a virtually constant supply of oxygen-rich blood to survive, an interruption in blood flow to the heart can quickly cause muscle cells to die.

Dead heart muscle cells cannot help the heart pump blood. Thus, people who suffer a heart attack are often left with “weak” hearts. Instead of strongly squeezing blood out of the heart to the rest of the body, a larger portion of the blood remains in the heart (i.e. reduced ejection fraction). People who have had a heart attack that reduces ejection fraction commonly develop a condition known as congestive heart failure.

People with congestive heart failure often have difficult lives. Congestive heart failure patients periodically experience exacerbations that require hospitalization. They are put on restrictive diets; their salt and fluid intakes are limited. They must also take several different medications to help the heart pump blood through the arteries to the body and keep fluid levels in the body low. These medications do not heal or replace dead heart muscle cells. Instead, they make the remaining cells work harder (or decrease resistance in the arteries, or help the body eliminate fluid through urination).

What is needed is a way to regenerate dead heart muscle cells. Fortunately, several research groups are working on ways to use stem cells to regenerate heart muscle cells so that heart attack patients can regain heart muscle function.

There have been at least 11 clinical trials studying the effects of stem cells on patients with myocardial infarction. The trials show that stem cell infusion into the vein, the coronary artery, or the heart muscle itself is safe and well-tolerated by patients. Notably among the studies, patients with acute myocardial infarction who received allogeneic human mesenchymal cells intravenously had a better ejection fraction, better heart structure, and better lung function after six months than those who received a placebo. In the APOLLO trial, patients with acute myocardial infarction who received adipose-derived mesenchymal cells had half the dead heart muscle cells than those who received a placebo (i.e. lesion volume was 50% lower in treated patients).

Phase III clinical trials are considered definitive (pivotal) evidence of benefit. In phase III C-CURE trial, patients with heart failure due to coronary artery disease received autologous mesenchymal cells (i.e. their own cells, specially prepared). Treated patients enjoyed significantly increased ejection fraction (heart-pumping ability) and better functional capacity and quality of life. Other Phase II clinical trials (ADVANCE, CONCERT-CHF, TRIDENT, POSEIDON-DCM) are ongoing.

These results are welcome news for patients who suffer—or will one day suffer—from a heart attack, an event that happens in 735,000 Americans every year.

 

 

 

Reference: Golpanian, S. et al. (2016). Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue. Physiological Reviews. 2016 Jul; 96(3): 1127–1168

Stem Cells from Elderly Patients Can Form New Bone

Stem Cells from Elderly Patients Can Form New Bone

Osteoporosis is a disease in which bones become weak, brittle, and are prone to fracture. While osteoporosis is commonly considered a disease of low bone density, it is more complex and extensive than that. New bone is constantly formed and destroyed (resorbed) throughout life. In osteoporosis, however, the rate at which it is resorbed accelerates, while the rate at which it is formed slows down. In other words, bone is being destroyed faster than it can be formed. This process changes the size and shape of bones and alters its microarchitecture (i.e. the structure of bone on a microscopic level).

Without screening, most people will not know that they have osteoporosis until they have a bone fracture. Bones simply get weaker until some minor trauma causes one or more bones to break. Fortunately, efforts to screen for the disease (e.g. DXA/DEXA or bone density scans) have helped doctors diagnose cases of osteoporosis before the disease progresses to the point of bone fracture.

The main treatment for osteoporosis is a class of drugs called bisphosphonates. Bisphosphonates block the cells that resorb bone (osteoclasts) to allow the cells that form new bone (osteoblasts) to catch up. While bisphosphonates are effective, many patients experience severe GI side effects from these drugs including reflux, esophagitis, and ulcers, and cannot take them.

In an effort to find new ways to treat osteoporosis and help patients who cannot tolerate bisphosphonates, researchers are exploring the possibility of using stem cells to treat the disease. Ideally, one would take stem cells from patients to help regrow bone. What has been unclear was whether a person with osteoporosis still has enough healthy stem cells to effectively regrow bone.

To test this, Dr. Jiang and colleagues collected stem cells from the fat tissue of patients with osteoporosis (i.e. adipose-derived stem cells). The researchers took these stem cells and encouraged them to grow and multiply for 14 days. After the stem cells had proliferated, they injected the cells into mice and studied the effects on bone growth. After 4 weeks, the researchers saw evidence on X-ray scans that adipose-derived stem cells caused new bone growth.

These results demonstrate that even patients with osteoporosis still possess stem cells that can be used to treat their own osteoporosis. While the stem cells need to be treated in a laboratory setting for 14 days, it is potentially possible to use a patient’s own stem cells to regrow bone and treat their osteoporosis.

The next phase of research will be to conduct a clinical trial to show test whether autologous stem cell treatment (injecting a patient with their own stem cells) can regrow bone in humans. While those clinical studies will be critical in determining whether this approach is practical and effective for patients, this laboratory research is very promising.

 

 

Reference: Jiang M. et al. (2014). Bone formation in adipose-derived stem cells isolated from elderly patients with osteoporosis: a preliminary study. Cell Biology International. 2014 Jan;38(1):97-105.

Using Stem Cells to Regrow Hair with Adipose-Derived Stem Cells

Using Stem Cells to Regrow Hair with Adipose-Derived Stem Cells

Alopecia, better known as hair loss, is a cosmetic problem. People do not need hair on their scalp to survive. Nonetheless, people with thinning hair or hair loss often endure considerable distress and suffering. Hair loss can cause low self-esteem, symptoms of depression, and a diminished quality of life. So while hair loss may be a simple cosmetic, strictly speaking, many people with alopecia struggle with an ongoing and serious problem.

Unfortunately, there are few effective treatments for hair loss. The two main medical treatments for hair loss are minoxidil and finasteride. Finasteride is generally only useful for male pattern baldness. Both men and women can use minoxidil, but it, too, is only partially effective. Various surgeries can be used to treat hair loss such as hair transplantation, scalp reduction, and scalp expansion, but patient satisfaction rates for these procedures are fairly low.

Stem cells that have been derived from fat tissue (i.e. adipose) secrete a number of beneficial chemicals called cytokines. These cytokines are important for wound healing and new blood vessel growth (i.e. angiogenesis). Cytokines released by adipose-derived stem cells are also able to stimulate hair follicles and induce the growth of hair. Based on these successes in the laboratory, dermatologists in Japan have used the substances secreted by adipose-derived stem cells to help people with hair loss.

Drs. Fukuoka, Narita, and Suga published a report detailing their successes in treating hair loss with proteins extracted from adipose-derived stem cells. A single hair loss treatment involves making a number of very small injections into the scalp. Each patient usually needs 6 to 8 treatment sessions, given once per month.

The doctors have performed this stem cell-based hair loss treatment on more than 1,000 patients and they have not encountered a single allergic reaction or infection. Indeed, no serious complications have occurred in their patients.

Not only is this stem cell-based hair loss treatment safe, but it is also apparently effective, as well. Patients have new growth of thin hair after two or three treatments, but this is minor and can usually only be detected by the doctors. After the fourth or fifth treatment, however, patients often notice new hair growth. By the sixth treatment, most patients can easily see new hair growth.

To confirm the effectiveness of their treatment, the doctors performed a half-side comparison test. In this test, they injected the stem cell-based hair loss treatment on one side of the scalp and injected saline on the other. The side of the scalp that received the stem cell extract had significantly more hair growth than the saline-treated side. This is strong evidence that the treatment is effective.

 

 

 

Reference: Fukuoka H. et al. (2017). Hair Regeneration Therapy: Application of Adipose-Derived Stem Cells. 2017;12(7):531-534.

Autologous Mesenchymal Stem Cell Transplantation for Spinal Cord Injury

Autologous Mesenchymal Stem Cell Transplantation for Spinal Cord Injury

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.

Reference

Satti et al. (2016). Autologous mesenchymal stromal cell transplantation for spinal cord injury: A Phase I pilot study.  International Society for Cellular Therapy, 18(4),518-522.

The Benefits of Stem Cells without the Cells

The Benefits of Stem Cells without the Cells

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.

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