Over the past few years, data has accumulated showing the promise for cell-based therapies to help in treating Inflammatory bowel disease with stem cells. Specifically, stem cells appear to offer the opportunity to overcome several weaknesses associated with conventional therapies that have targeted perianal Crohn’s disease.
Based on these positive results, scientists and healthcare providers have become more adamant about understanding the broader role stem cells could play in the treatment of all inflammatory bowel disease. A new review published in Current Gastroenterology Reports discusses this specific issue and offers insights into the direction of stem cell research as it relates to inflammatory bowel disease.
The authors of this review discuss data from over a dozen clinical trials that have already been conducted on the impact of stem cell therapies in Crohn’s disease. Thus far, much of the success of regenerative medicine for the treatment of Crohn’s disease has been for the specific treatment of perianal Crohn’s disease, which occurs when the digestive and gastrointestinal inflammation associated with Crohn’s disease extends to the anal area.
Given the frequency with which the lining of the intestine is inflamed in inflammatory bowel disease, including both perianal Crohn’s disease and non-perianal Crohn’s disease, research efforts are focusing more and more on how stem cells may be able to combat this type of luminal disease. The authors put forth suggestions for the types of information that researchers should aim to obtain if we are to adequately treat intraluminal disease with regenerative medicine.
The potential of stem cells to address inflammatory bowel disease that has been demonstrated so far provides hope that this type of strategy will help not only patients with perianal Crohn’s disease but those with other forms of inflammatory bowel disease as well. More research should help to determine if and how these therapies can be deployed to help this patient population.
Reference: Lightner, A.L. (2019). Stem cell therapies for inflammatory bowel disease. Current Gastroenterology Reports, 21(4), 16.
Researchers have recently established that a hallmark of Amyotrophic Lateral Sclerosis (ALS) is endothelial cell degeneration that leads to vascular pathology. When this vascular pathology occurs, damage develops to the barrier between the blood and the central nervous system. Given this new understanding of the pathophysiology of ALS, researchers have begun looking at the potential of repairing this barrier as a strategy for treating the disease with bone marrow stem cells.
A recent study, published in Scientific Reports, addressed this issue by testing how human bone marrow cells may impact blood-spinal cord barrier repair by transplanting these cells in an ALS model. The researchers hypothesized that the cells should help to repair the barrier, reversing the damage accompanying ALS. They were also interested in whether this type of repair may improve not only the integrity of the barrier between the blood and central nervous system but also improve symptoms of ALS.
What the researchers found was that the human bone marrow cells differentiated into the type of endothelial cells that were needed for repair and successfully engrafted into the capillaries of the spinal cord in their model. Several specific observations led the scientists to conclude that these stem cells helped to effectively restore the barrier between the blood and the spinal cord.
The stem cells improved the integrity and survival of nervous system cells, including astrocytes and spinal cord motor neurons, preventing problematic changes in these cells that are associated with the breakdown of the blood-central nervous system barrier. Critically, the implantation of the stem cells also led to improvements in behaviors associated with ALS.
While there is still a lot of research to be done to establish whether bone marrow stem cells can help repair the blood-spinal cord barrier in patients with ALS, this study provides promising data. Given that there is no cure for ALS and limited treatment options, there is likely to be an emphasis on cell-based therapies for the disease. As more data become available, we will get a clearer picture as to if and how stem cells can help ALS patients.
Reference: Garbuzova-Davis,S. (2017). Endothelial and astrocytic support by human bone marrow stem cell grafts into symptomatic ALS mice towards blood-spinal cord barrier repair. Scientific Reports, 7(884).
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. A new and unique treatment is the use of stem cells to treat Perianal Crohn’s Disease.
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.
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. Many medical professionals are pondering the question of how stem cells may help those with chronic pain.
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.
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. There has been much talk in the medical community of using stem cells to rebuild the heart after a heart attack.
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
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.
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