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Exosomes and Their Critical Role in Stem Cell Therapy

Exosomes and Their Critical Role in Stem Cell Therapy

Much of the medical research and clinical applications of stem cell therapy have thus far focused on stem cells and their potential to repair damaged or diseased tissue that has not responded to conventional therapies. Though there has been a lot of evidence to suggest that the use of certain types of stem cells can be safe, experts have suggested that strategies for therapy using exosomes that can avoid the use of living stem cells may provide an even better opportunity to slow the progression of various diseases.

Paracrine secretions have been shown to play a significant role in the ability of stem cells to improve disease conditions, and exosomes are a key element of these secretions. From a functional standpoint, exosomes enable stem cells to transfer their genetic information to other cells residing in the damaged tissue.

Because these are responsible for some of the critical benefits of stem cells, researchers have speculated that the use of exosomes rather than stem cells may provide specific advantages in some therapeutic contexts. A review in Stem Cells International has provided a comprehensive overview of what is known so far about the potential role of exosomes in stem cell therapy.

Exosomes are released from a wide variety of stem cell types and influence the functioning of nearby cells and tissues. Their use  alone may offer better therapeutic results. Indeed, they have shown particular promise in addressing symptoms of many conditions.

Researchers are hopeful that exosomes will be able to help patients in new and innovative ways, more research is needed to determine the best way to apply them in stem cell therapy.

 

Reference: Han, C. et al. (2016). Exosomes and their therapeutic potentials of stem cells. Stem Cells International, 1-11.

How Exosomes Can Improve Stem Cell Therapy

How Exosomes Can Improve Stem Cell Therapy

Given the limitations of several conventional methods to treat a wide variety of diseases and injuries, stem cell therapy has begun to gain in popularity. The evidence supporting the field of Regenerative Medicine, which involves using stem cells to regenerate healthy, functional tissue, has indeed been accumulating in recent years.

There are a number of different types of stem cells that have been explored for their therapeutic potential. Mesenchymal stem cells have become a preferred option for therapy because of their ability to differentiate into several different types of adult tissue and to be transplanted safely and effectively into patients.

One-way mesenchymal stem cells confer their therapeutic benefits is through paracrine effects that are achieved by the secretion of extracellular vesicles, some of which are exosomes. Exosomes are between 30 and 100 nanometers (nms) in diameter and exist in blood, cerebrospinal fluid, and other bodily fluids.

A recent review, published in Cell Transplantation, covered research showing that mesenchymal stem cell exosomes are therapeutically advantageous for the management of several conditions, including Parkinson’s disease, osteoarthritis, and stroke.

The review discusses, for instance how in models of Parkinson’s disease, exosomes have been shown to provide neuroprotection. MSC-derived exosomes also appear to inhibit inflammation in the context of osteoarthritis and also to stimulate repair in damaged tissue. Further, specific exosome biomarkers, miR-9 and miR-124, have proven to be promising in diagnosing the severity of stroke.

Based on recent research covered in this review, stem cell-derived exosomes have significant therapeutic potential. Though this review focuses specifically on the relevance of exosomes in Parkinson’s disease, osteoarthritis, and stroke, exosomes will likely provide benefits for patients in a variety of contexts and will prove to be an important part of Regenerative Medicine.

 

 

Reference

Chang, Y-H, et al. (2018). Exosomes and stem cells in degenerative disease diagnosis and therapy. Cell Transplantation, 27(3), 349-363.

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.

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.

Fighting Against Tissue Injury: Stem Cell Exosomes

Fighting Against Tissue Injury: Stem Cell Exosomes

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.

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