Promising Data for the Use of Stem Cells to Treat Perianal Crohn’s Disease is Accumulating

Promising Data for the Use of Stem Cells to Treat Perianal Crohn’s Disease is Accumulating

Crohn’s disease, a form of chronic inflammatory bowel disease, affects an estimated 700,000 people in the United States, affecting men and women equally. While the disease is characterized by abnormal inflammation in the gastrointestinal and digestive tracts, some people with the illness develop perianal Crohn’s disease. In this case, the inflammation extends to areas around the anus. The precise proportion of Crohn’s disease patients who develop perianal Crohn’s disease is debated, but the need for better treatments for the condition is not.

Unfortunately, though there are several drug and surgical interventions that have been developed to treat perianal Crohn’s disease, each of the available treatment options suffers critical limitations, including risks for adverse side effects.  There is no available therapeutic approach that successfully achieves long-term remission.

Based on the need for – and lack of – more efficacious interventions for perianal Crohn’s disease and the ability of cell-based therapies to address similar types of disease, researchers have positioned that stem cell therapy may be a promising avenue for the relevant patient population. A recent review published in the Journal of Crohn’s and Colitis covers the research that has been conducted to address this possibility and the data that suggest that mesenchymal stem cells could provide a safe and effective way to treat perianal Crohn’s disease without the unwanted side effects associated with conventional treatment options.

In this review, the authors cover clinical trials on cell-based therapies for perianal Crohn’s disease, including phase 1, phase 2, and phase 3 randomized controlled trials. The authors consider the differences in outcomes between conventional treatments and cell-based therapies and offer suggestions for the direction of research into the use of stem cells for the treatment of perianal Crohn’s disease.

 

 

Reference: Lightner, A.L. & Faubion, W.A. (2017). Mesenchymal stem cell injections for the treatment of perianal Crohn’s disease: What we have accomplished and what we still need to. Journal of Crohn’s and Colitis, 11(10), 1267-1276.

How Stem Cells May Help Those with Chronic Pain

How Stem Cells May Help Those with Chronic Pain

A review in the Journal of Stem Cell Research & Therapy has summarized an array of studies that demonstrate that a specific type of stem cell – the mesenchymal stem cell – may be beneficial as a therapeutic approach to chronic pain. The authors point to the huge burden of chronic pain. It is estimated that more than 115 people suffer from the condition, which is more than those who suffer from diabetes, stroke, cancer, and coronary heart disease combined.

Chronic pain is also associated with significant losses in productivity. Given how extreme the burden of chronic pain has become, the National Institute of Medicine has suggested that finding effective ways to alleviate chronic pain should become a priority for the nation.

Regenerative medicine has offered an effective way to treat a variety of injuries and diseases, including some that are related to chronic pain. As the term “regenerative medicine” implies, much of the research into the clinical effects of stem cells have shown that they lead to beneficial outcomes by regenerating damaged tissue by replacing that tissue with new cells.

This new review looks at the potential of mesenchymal stem cells to specifically improve chronic pain through the ability of the cells to suppress inflammation. Given that inflammation is a common characteristic of conditions associated with chronic pain, a strategy that addresses this phenomenon could represent an effective way to help those with chronic pain that comes from things like degenerative disc disease and osteoarthritis.

The current approaches to chronic pain are limited in their ability to reduce or control pain, so there is a great need to develop more effective therapies. Research thus far into the potential impact of mesenchymal stem cells on chronic pain has provided promising results regarding effectiveness and safety. Specifically, these stem cells have not been associated with adverse side effects, they lead to the development and growth of healthy tissue, and they appear to provide pain relief. Future research will help to clarify the mechanisms by which mesenchymal stem cells may confer their benefits to those with chronic pain and provide new insights into how can best use these cells to help chronic pain sufferers.

 

 

Reference: Waterman, R.S. & Betancourt, A.M. (2011). Treating chronic pain with mesenchymal stem cells: A therapeutic approach worthy of continued investigation. Journal of Stem Cell Research & Therapy, S2, 1-5.

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

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.

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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