Using Exosomes to Treat Kidney Diseases: State of the Research

Using Exosomes to Treat Kidney Diseases: State of the Research

Kidney diseases are among the most expensive and most debilitating diseases. Total costs are in excess of $50 billion a year, with $30 billion spent on people with end-stage renal disease including hemodialysis and kidney transplantation. People with kidney diseases have diminished quality of life, and substantial amounts of their time are devoted to medical treatment. Not surprisingly, researchers are aggressively pursuing novel therapies to treat kidney diseases before they result in end-stage renal disease. Stem cells and exosomes are among the most exciting and the most promising research topics in this area.

Most cells release tiny packets called extracellular vesicles. The most notable extracellular vesicles are exosomes. While small, exosomes are filled with high concentrations of potentially helpful substances such as RNA, DNA, and proteins. While most cells release exosomes, researchers are particularly interested in exosomes released by stem cells. It is within these exosomes that stem cells pass along the substances that make stem cells helpful in tissue repair and regeneration.

Zhang and coauthors reviewed the recent advances that have been made using exosomes to treat kidney diseases. Most of the work has focused on acute kidney injury or AKI.  Acute kidney injury can lead to chronic kidney disease and kidney failure. Thus, if one could stop AKI, they could potentially reduce the risk of chronic kidney disease.

Many different research groups have shown the power of exosomes and other extracellular vesicles in treating acute kidney injury. Exosomes taken from mesenchymal stem cells protected kidney cells from cell death and fibrosis and helped them repair themselves. The same was true of exosomes derived human umbilical cord stem cells. Even stem cells taken from human liver cells were able to improve kidney function after injury. There are many other examples.

Gatti et al. reported that extracellular vesicles derived from human adult mesenchymal stem cells could protect against acute kidney injury, but, most impressively, also halted the progression of AKI to chronic kidney disease. This finding has important implications for people who suffer from serious acute kidney illnesses, such as kidney ischemia. It means that—if confirmed in human studies—stem cell-derived extracellular vesicles can help treat kidney disease in the short term and reduce the risk of that illness becoming a chronic, debilitating problem.

Further research is needed in this field but, initial results confirmed by many laboratories have created well-founded enthusiasm for the future.

Reference: Zhang, W. et al. (2016). Extracellular vesicles in diagnosis and therapy of kidney diseases. American Journal of Physiology – Renal Physiology. 2016, Nov 1; 311(5): F844-F851.

Mesenchymal Stem Cell Treatment for ALS is Safe and Feasible

Mesenchymal Stem Cell Treatment for ALS is Safe and Feasible

Amyotrophic lateral sclerosis or ALS is a devastating, progressive neurological disease. While the precise cause is unknown, ALS does destroy nerve cells in the spinal cord, which causes several debilitating symptoms. Often the first symptom of ALS is weakness in the hands or arms that is usually more pronounced on one side of the body. As more spinal cord nerve cells become dysfunctional and die, patients with ALS become weaker, their movements grow slower, and their muscles begin to atrophy (i.e. break down). At the same time, some muscles in the limbs become spastic, which means they are constantly in a contracted state. In later stages of ALS, patients have difficulty swallowing and breathing. Mesenchymal Stem Cell Treatment for ALS is a unique and new option.

The only drug to have any known survival benefit in ALS is riluzole. Patients who take riluzole live longer than those who do not; however, the drug does not improve function or meaningfully reduce symptoms. The only other approved ALS treatment, edaravone, may slow the rate at which ALS gets worse. However, neither of these drugs is a cure—far from it, in fact. Indeed, doctors and patients are left with virtually no effective treatment options for ALS.

Because ALS is caused by the destruction of nerve cells in the spinal cord, the regenerative properties of stem cells may offer a solution. The hypothesis is that stem cells—and exosomes collected from stem cells—can help protect, preserve, or even regenerate cells that are affected by ALS.

A flurry of research has been published over the last decade documenting the safety and possible effectiveness of mesenchymal stem cells for the treatment of ALS. In 2009, Deda et al. showed bone marrow stem cells injected into the spinal area were safe in patients with ALS, even showing that some patients had improvements in neuromuscular testing. The research groups of Karussis, Mazzini, Blanquer, and Baek showed similar safety results. Martinez et al. showed that stem cells derived from bone marrow could improve survival in patients with ALS. Rushkevich et al. showed that stem cell infusion improved the quality of life in patients with ALS.

While more work is clearly needed to determine the full effectiveness of stem cell treatment for ALS, the number of researchers working on this topic and the number of successful studies published in this area are reasons for hope. These clinical studies show that stem cell treatment for ALS is clearly safe and feasible. What is needed are larger clinical trials that specifically focus on the effectiveness of treatment, both in the near- and long-term.

Reference: Roberta Bonafede and Raffaella Mariotti. (2017). Stem cell mobilizers: ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles. Frontiers in Cellular Neuroscience. 2017; 11:80.

Exosomes Help Regenerate Intervertebral Disc Tissue: Implications For Degenerative Disc Disease

Exosomes Help Regenerate Intervertebral Disc Tissue: Implications For Degenerative Disc Disease

The spinal column is made up of more than a dozen vertebral bones stacked on top of each other. Since the spine is not a single bone, it is capable of pivoting and bending, which gives the torso a degree of flexibility. A key part of this structure relies on the substance between the vertebral bones called the intravertebral disc.

The intravertebral disc is made up of the annulus fibrosis (the tough outer ring) and the nucleus pulposus (the jelly-like inner core). Each intervertebral disc acts as a shock absorber between the vertebral bones. Over time and with age, however, the intervertebral disc tends to breakdown. This can cause called degenerative disc disease, which includes herniated discs (“slipped discs”), pinched nerves, neck and back pain, and nerve problems.  Obviously, finding ways to reverse or prevent intravertebral discs from breaking down is of great medical and scientific interest and for the countless patients with degenerative disc disease.

As with other groups interested in regenerative medicine, researchers have turned to stem cells in an effort to regenerate tissue within the intravertebral disc. One research group reported their recent success using bone marrow-derived mesenchymal stem cells. The scientists collected exosomes—very small packets filled with highly concentrated molecules such as proteins, microRNA, transcription factors and lipids—from these stem cells. In this study, researchers also collected exosomes from nucleus pulposus cells and tested the exosomes in various ways.

The researchers found that exosomes could send out signals to bone marrow mesenchymal cells and call them to the intervertebral disc. The exosomes also prompted the stem cells to become new nucleus pulposus-like cells. Conversely, exosomes from bone marrow mesenchymal cells caused nucleus pulposus cells to grow and multiply (i.e. proliferate). Finally, exosomes helped the tissue in degenerating vertebral discs to express the same genes as healthy discs.

While these results are complex, they suggest that exosomes from bone marrow mesenchymal cells and nucleus pulposus cells work together to recruit and make more healthy cells in degenerating vertebral discs. This could have profound implications for the millions of people with degenerative disc disease. If these results are confirmed in clinical trials, it would mean that exosomes could be used to prevent or reverse degenerative disc disease. We anxiously await further work in this exciting field.

 

 

Reference: Kang L. et al. (2017). Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells. Stem Cell Research Therapy. 2017; 8: 108.

The Potential for Exosomes to Help Patients with Arthritis

The Potential for Exosomes to Help Patients with Arthritis

The field of Regenerative Medicine has shown great promise for helping those with a variety of chronic diseases, including arthritis. Indeed, data on the potential value of using stem cells to address issues relating to arthritis have been growing. While specific stem cells like mesenchymal stem cells have demonstrated therapeutic effects in models of arthritis and other inflammatory diseases, the specific ways in which these cells confer their benefits are not yet well understood. Given that these stem cells contain different types of elements, it is important that research establishes which of these elements is critical to the therapeutic properties of stem cells.

A recent study, published in Theranostics, looked specifically at the different effects that small exosomes and larger microparticles from within mesenchymal stem cells have on the inflammatory processes that occur in arthritis. To conduct their experiment, scientists isolated the exosomes and microparticles from mesenchymal stem cells using an ultracentrifugation technique and then exposed the exosomes and the microparticles to cells of the immune system – specifically, T and B lymphocytes, which are implicated in arthritis.

What the researchers found was that, in their models of arthritis, both the exosomes and the microparticles suppressed the T lymphocyte proliferation that is indicative of inflammation. However, unlike microparticles and even parental mesenchymal stem cells, the exosomes were also able to induce other anti-inflammatory effects. The result of exosome activity was, therefore, more efficient blunting of inflammation.

These results point to the potential of not just stem cells, but specifically the exosomes of these cells, in therapeutically addressing inflammatory arthritis. While more research is needed to understand how these exosomes could actually impact arthritis patients, these data provide hope that stem cells and even just elements of stem cells will help these patients by improving their ability to combat problematic inflammation.

 

Reference: Cosenza, S. et al. (2018). Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis. Theranostics, 8(5), 1399-1410.

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.

Mesenchymal Stem Cell Exosomes Promote Periodontal Regeneration

Mesenchymal Stem Cell Exosomes Promote Periodontal Regeneration

Periodontal disease, better known as gum disease, is very common. About half of all adults have chronic gum disease, and as many as 15% had severe periodontal disease. In periodontal disease, the gums become red and inflamed. The tissues that connect the tooth to the bone, such as the periodontal ligament, are damaged or destroyed. Chronic periodontal disease can even invade and destroy jaw bone. Making matters worse, as the gums recede, they can collect bacteria in spaces called periodontal pockets. Over time, these periodontal pockets can become dental abscesses. As the gums become more and more diseased, the affected tooth or teeth may fall out.

The treatment for periodontal disease varies depending on its severity. Good oral hygiene including regular brushing and flossing can reverse mild periodontitis. A dentist can deeply clean, probe and disrupt periodontal pockets. In more severe cases, topical antiseptics or oral antibiotics may be required. Less often, a dental surgeon must remove diseased areas of gum and bone.

Periodontitis usually chronic and causes significant ongoing inflammation. Thus, the gums take a long time to heal. In many cases, periodontal disease can be difficult to treat.

Fortunately, dental researchers have been exploring ways to use mesenchymal stem cells to help the healing process. More specifically, they have been using the exosomes released by mesenchymal stem cells. Exosomes are small packets of proteins, RNA, and other molecules that help promote growth and tissue regeneration. Since exosomes are not cells, they are much easier to collect, store, transport, and administer to patients. Most importantly, exosomes appear to contain all of the things that make stem cells so powerful in regenerative medicine.

In a 2019 study, Dr. Chew and colleagues used exosomes collected from mesenchymal stem cells to treat rats with periodontal disease. The researchers noticed that animals treated with exosomes healed much faster than untreated animals. Exosomes taken from mesenchymal stem cells promoted periodontal tissue regeneration helped grow new bone and regrew periodontal ligaments. The researchers also found that exosomes were able to recruit new cells to replace the damaged ones.

This scientific research is an exciting breakthrough in the fields of dentistry and periodontics. Chew and co-authors have shown that mesenchymal stem cell exosomes could enhance periodontal tissue regeneration without any adverse effects. The scientists go on to state that these findings will serve as the basis for future “cell-free” exosome treatments for periodontal disease. This is certainly good news for the more than 150 million Americans with periodontitis.

 

 

Reference: Chew, JRJ. et al. (2019). Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration. Acta Biomaterialia. 2019 Apr 15;89:252-264.

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