Patients usually recover from bone fractures with the right treatment, but sometimes the bone fails to heal because new tissue does not form and connect the broken pieces properly. Delayed union refers to cases where the bone takes longer than usual to heal, and nonunion refers to cases where the bone does not heal. In approximately 5 to 10 percent of cases of a fractured bone, delayed union or nonunion occurs. These conditions are associated with long-term pain and discomfort, and though can be addressed through surgical treatments, these interventions do not always lead to long-term healing.
In recent years, researchers have begun exploring the potential for mesenchymal stem cells to help address these important challenges of delayed union and nonunion. A review of the potential for these stem cells to help in these cases where fractures do not properly heal was recently published in the Journal of Biomedical Materials Research.
Mesenchymal stem cells are helpful in bone healing because they differentiate well and can differentiate into different cell lineages that are all important for bone formation, growth, and maintenance. These cell types include chondrocytes, osteoblasts, myoblasts, and adipocytes.
According to the authors of the review, mesenchymal stem cells can be used in conjunction with extracellular matrix scaffolds and biological adjuvants that promote growth, differentiation, and blood vessel formation, to help in the bone healing process when the delayed union or nonunion occurs. Future research will help to determine the best ways that mesenchymal stem cells can be used in combination with bioengineering strategies to help patients whose bone fractures do not heal or do not heal properly.
Traumatic brain injury (TBI) is one of the most common causes of disability in the United States, affecting over 13 million citizens. Traumatic brain injury is responsible for over 2 million emergency department visits, over a quarter of 1 million hospitalizations, and nearly 60,000 deaths each year.
Traumatic brain injury harms brain tissue in two phases. The first phase of injury occurs at the time of the traumatic incident. This initial injury may cause small or large areas of the brain to bleed. It may also shear (stretch/tear) nerve cells, making them dysfunctional. The second phase occurs hours or days after the initial injury. The brain is subjected to ongoing damage because of inflammation, cell death, and injury to blood vessels. Many people with TBI are left with lifelong problems with thinking, memory, and behavior.
In both of these phases of injury, one major way to help prevent long-term brain damage is by maintaining adequate blood flow to brain tissue. Unfortunately, once the damage has occurred, it can be a challenge to reverse the damage. Patients usually must endure months or years of physical and occupational therapy to regain what was lost. Moreover, patients often need substantial amounts of psychiatric and psychological support to treat mental health problems.
Fortunately, researchers are using hyperbaric oxygen therapy (HBOT) to improve blood flow to the brain in patients with traumatic brain injury. Hyperbaric oxygen therapy provides patients with pure oxygen (100%) at slightly higher pressures than they would experience normally. It is been used for hundreds of years to treat scuba divers who suffered “the bends” or decompression sickness; however, researchers are finding that hyperbaric oxygen therapy is a “coveted neurotherapeutic method for brain repair.”
To study the effects of hyperbaric oxygen therapy, researchers selected 10 people who had suffered mild traumatic brain injury in the previous 7 to 13 years. Patients all had brain damage that interfered with attention, memory, and thinking abilities.
Even though patients had sustained traumatic brain injury and brain damage a decade earlier, hyperbaric oxygen therapy was able to improve blood flow in the brain. Likewise, the amount of blood detected within the brain significantly increased, suggesting that hyperbaric oxygen therapy actually caused blood vessels in the brain to grow and multiply. Just as impressively, patients with chronic brain damage performed better on tests of cognition (i.e. thinking). They were able to process information more quickly, they had better motor function, and they were able to take in and process information about the world around them more efficiently.
Because people with traumatic brain damage have limited treatment options to improve their situations, these results are incredibly exciting. This was a study on 10 patients and more studies on larger numbers are still needed to build on these findings. Nonetheless, these results are quite encouraging for people with traumatic brain injury and their loved ones.
Crohn’s disease is a chronic inflammatory bowel disease that has no cure. It causes abdominal pain, frequent diarrhea, weight loss, fatigue, and anemia. While the disease can be controlled to some degree through oral and injectable medications, life-threatening complications may occur.
One of the feared complications of Crohn’s disease is called a bowel fistula. A fistula is an abnormal connection between two places on the body. In Crohn’s disease, a fistula forms between the intestine and some other structure—the intestine essentially forms a “tunnel.” The fistula can form between one loop of intestine and another, between intestine and bladder, or even between the intestine and the outside of the body. This complication of Crohn’s disease is obviously quite distressing to patients.
Some bowel fistulas may close on their own with conservative treatments, but fistulas associated with Crohn’s disease do not respond well to available medical treatments. Those looking for an alternative treatment may be able to consider stem cell therapy.
Stem cells offer an interesting potential solution to this problem. Stem cells can provide a large dose of normal cells filled with molecules that can help direct normal bowel growth and development. Indeed, researchers have shown that autologous mesenchymal stem cells can help close and heal fistulas in patients with Crohn’s disease.
In phase I, II, and IIB clinical trials, stem cells derived from adipose tissue or bone marrow were directly infused into the bowel area (via a so-called intra-fistular injection). Across five clinical studies including over 100 patients, stem cell administration resulted in complete fistula healing in 50 to 80% of patients treated. Of those who did not obtain complete control fistula closure, almost all had evidence of improvement. These results support that autologous mesenchymal stem cell therapy is a promising future treatment for patients with Crohn’s disease and may offer patients enjoy a better quality of life.
Ulcerative colitis and Crohn’s disease, together known as inflammatory bowel disease, are chronic disorders of the lower digestive tract that cause patients considerable difficulty and discomfort. Patients generally go through periods of normalcy punctuated by relapses. In cases of inflammatory bowel disease, patients may experience severe, and sometimes bloody diarrhea. Patients also experience crampy abdominal pain, the urgent need to defecate, pain with defecation and even fecal incontinence. Consequently, people with inflammatory disease often endure substantial amounts of suffering.
Inflammatory bowel disease is usually treated with 5-aminosalicylate or sulfasalazine. These drugs are intended to reduce inflammation in the bowels. Relapses do still occur for those patients taking these medicines. During these relapses, patients often need to take steroids for short or intermediate periods of time but over time, side effects can occur. Immunomodulators such as azathioprine, 6-mercaptopurine, and methotrexate can be used to reduce inflammation, however, these drugs can also cause side effects. Newer biologic response modifiers have helped people with severe inflammatory bowel disease but they may weaken the body’s immune system, making it more difficult to fight off infection. For these reasons, safer and more effective treatments for inflammatory bowel disease are needed.
Fortunately, researchers have conducted a number of clinical studies examining the role of stem cells in the treatment of inflammatory bowel disease. The most promising results have come from allogeneic mesenchymal stem cell therapy using stem cells derived from the umbilical cord. Research has found that allogeneic mesenchymal stem cells injected into a vein were able to induce a clinical response 3 out of 9 patients tested. One patient had complete clinical remission. In all cases, the stem cells increased the quality of life for patients. Five out of seven patients with inflammatory bowel disease had clinical remission after stem cell treatment. Likewise, further research showed that the stem cells could induce a clinical response and 12 of 15 patients and full clinical remission in eight of them. Here too, patients reported improved quality of life with stem cell treatment.
These results are incredibly promising and offer hope to patients struggling with ulcerative colitis and Crohn’s disease. While more research is needed, patients with inflammatory bowel disease should follow this field closely for new developments.
Silicosis, which is also known as miner’s phthisis, potter’s rot grinder’s asthma, potter’s rot, is an occupational disease of the lungs that is caused by the inhalation of a specific type of dust called crystalline silica dust. The disease causes inflammation and scarring in the lungs that leads to the formation of lesions. The disease has been increasing in incidence in developing countries in recent years and unfortunately cannot be fully cured.
A recent study, published in Stem Cell Research & Therapy, explored, for the first time, the potential to intervene in processes associated with silicosis. Stem cell therapy has been used to address inflammation and the resulting tissue damage. Mesenchymal stem cells have been applied to other occupational conditions as well. The researchers hypothesized that adipose-derived mesenchymal stem cells would improve pulmonary fibrosis by reducing inflammation.
Through their study, they found that using these adipose-derived mesenchymal stem cells in silicosis did indeed lead to a remissive effect with regard to pulmonary fibrosis. Further, they found that this occurred by reducing inflammation by modifying protein certain cellular pathways that decreased the expression of problematic proteins.
While this data is preliminary, they show the potential promise of stem cells in the therapeutic intervention of silicosis. Future studies will help researchers and clinicians better understand how stem cells can be used to combat the pulmonary fibrosis associated with silicosis, as well as how they can be used to combat other occupational diseases.
While most approaches to stem therapy involve infusing purified stem cells into the body, Thom and fellow researchers have shown that hyperbaric oxygen therapy (HBOT) is capable of stimulating the body to produce its own stem cells. Thom, Heyboer, and co-authors have extended this work by showing that by slightly increasing the pressures used during hyperbaric oxygen therapy, one can significantly increase the number of stem cells produced.
In his original work, Thom and colleagues showed that a single, two-hour session of 2.0 atmospheres (atm) pressure (twice the air pressure we normally feel at sea level) was capable of doubling the number of stem cells in the bloodstream. Twenty treatments increased stem cell levels by 800%. To study this phenomenon more closely, Thom’s research group recruited 20 patients to undergo hyperbaric oxygen treatment, some at the original 2.0 atm pressure, and some at 2.5 atm. The primary goal of this research was to find out whether a higher pressure was capable of eliciting a greater number of cells.
As before, treatment with 2.0 atm of hyperbaric oxygen substantially increased the number of stem cells found in the blood. However, treatment with 2.5 atm doubled or even tripled the number of stem cells produced compared to the 2.0 atm treatment session. In other words, a slightly higher pressure causes the body to produce substantially more of its own stem cells.
Researchers focused on two types of stem cells, in particular, CD34+ and CD45-dim—markers that appear on stem cells and/or progenitor cells. They are primarily found on cells in the bone marrow. Stem cells with CD45-dim generally go on to become bone, blood, or blood vessel cells, while CD34+ cells can differentiate into almost any cell. Hyperbaric oxygen therapy is thought to stimulate the bone marrow to produce and release these stem cells into the bloodstream, which is the reason these treatments raise stem cell levels in the blood.
The results published by Thom and coworkers suggest that patients who wish to enhance the number of stem cells should consider undergoing hyperbaric oxygen therapy. Furthermore, the greatest number of stem cells was observed after 20 treatment sessions, suggesting that a greater effect occurs with more treatments.
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