Liver failure is a serious, potentially fatal condition in which large swaths of liver cells become dysfunctional and die. Liver failure is the result of several conditions including chronic alcohol consumption, exposure to drugs that are toxic to the liver (e.g. acetaminophen), autoimmune diseases, or infections such as hepatitis C. Liver failure causes several metabolic abnormalities including dangerously low levels of sodium, potassium, and phosphate in the blood. Moreover, four in 10 people with liver failure have trouble regulating their blood glucose levels, which can cause profound hypoglycemia. Since the liver detoxifies the blood, when the liver fails, patients can experience confusion from excessive amounts of ammonia and other substances in the blood. Seizures are also possible.
Short of liver transplantation, there are very few treatments for liver failure. Most treatments focus on restoring sodium, potassium, phosphate, and glucose levels in the blood, and bringing down ammonia levels. Fortunately, experiments show that human mesenchymal stem cells may be a promising treatment for liver failure.
Researchers enrolled 43 people with acute-on-chronic liver failure caused by hepatitis B infection. In this group, 24 patients were treated with mesenchymal stem cells derived from human umbilical cord and 19 patients received a saline solution. The groups received stem cells or placebo, respectively, three times every four weeks. Patients treated with mesenchymal stem cells showed better measures of liver function than those who received placebo. Livers of the patients treated with stem cells produced much more protein, albumin, and clotting factors, and were better able to process bilirubin. Importantly, no significant side effects were observed during the trial.
Given the serious nature of liver failure and the lack of effective treatments (besides liver transplant), this research is incredibly exciting. It offers hope that through further research scientists will be able to use mesenchymal stem cells to change the outcomes of people with acute-on-chronic liver failure.
The human skeleton is made up of bone, cartilage, fat, nerves, blood vessels, and bone marrow. While the skeleton is usually strong and vibrant in youth, it changes considerably with age. Many people, especially women, experience demineralization of bone called osteoporosis. Most of us will suffer from painful, stiff, arthritic joints either from osteoarthritis or rheumatoid arthritis or both. While some of the diseases of bone and joints have specific treatments, none of them helps to restore bone and joints to their younger state. If one could reintroduce skeletal stem cells into the body, that could all change. Excitingly, researchers have recently isolated human skeletal stem cells from bone and other tissues.
At first glance, this breakthrough may not seem so surprising. One might wonder: didn’t we already have stem cells that form bone and cartilage? The answer is yes, but with an important caveat. Before researchers recently isolated human skeletal stem cells, the only stem cells that could be used to produce bone and cartilage were rather unpredictable. In addition to bone and cartilage, the mesenchymal stem cells that have been long used to form these tissues could also produce fat, muscle, fiberglass, blood vessel cells, and other tissues. In other words, the stem cells were broadly multipotent and, by extension, could not easily be used for a specific purpose, like mending bone or repairing an arthritic joint. That is why the recent discovery of these particular skeletal stem cells is so important.
The researchers isolated skeletal stem cells from various human tissues, mainly bone. They then used the skeletal stem cells to regrow bone and/or cartilage. Not only did the stem cells produce bone and cartilage in the first animal they tested, but they could retrieve stem cells from that animal and then cause bone to regrow in a second animal. This means that the skeletal stem cells have the capability of reproducing themselves.
The same researchers also discovered that when a skeleton is injured, such as in a bone fracture, the number of skeletal stem cells in that area increases dramatically. This makes sense since these cells are used to repair and regrow bone. It is also a promising result because it suggests that stem cells could be used to accelerate bone and joint healing in humans.
Scientists not directly involved in this research heralded this finding as “an extremely important advance.” However, they also acknowledge that more work needs to be done before skeletal stem cells can be routinely used in patients with orthopedic conditions. Nevertheless, these results are an exciting development in the field of stem cell research and orthopedics.
Spinal cord injury is the second leading cause of paralysis in the United States. When the spinal cord is severely injured, nerve cells in the spinal cord are damaged or destroyed. Also, a sort of scar forms in the affected area, which prevents nerve signals from traveling between the brain and the extremities. Consequently, people who sustain spinal cord injuries suffer from paralysis. The degree of paralysis depends on the location of the spinal cord injury; injuries higher on the spinal cord such as the neck or upper back area can lead to paralysis of all four limbs, for example. In almost all cases, the paralysis is permanent once it occurs, because nerve cells in the spinal cord do not regenerate.
Because spinal cord injuries are common and the consequences are usually permanent, researchers have been aggressively and tirelessly researching ways to treat this condition. One approach is to try to form new nerve cells in the spinal cord using stem cells. Mesenchymal stem cells can become new nerve cells given the right set of circumstances. Unfortunately, simply injecting mesenchymal stem cells into patients with severe spinal cord injuries cannot reverse paralysis. On the other hand, using exosomes from mesenchymal stem cells may be the push that stem cells need to become nerve cells in the spinal cord.
Exosomes are tiny packets of cellular material released by stem cells. They contain a variety of potentially beneficial substances; perhaps the most important in cell regeneration is micro RNA (miRNA). miRNA can cause complex changes in cells that simple drugs, proteins, or even regular RNA cannot. Researchers cannot easily deliver miRNA to where it is needed in the body, but exosomes taken from stem cells can deliver miRNA right where it needs to be.
Researchers collected human mesenchymal stem cells and placed them in an environment that would cause them to become nerve cells. But instead of simply using the stem cells directly, they instead collected the exosomes from those stem cells. Those exosomes could then be used to prompt mesenchymal stem cells to become nerve cells. Simply put, the exosomes drove the process more efficiently than the stem cells alone.
What does this all mean? Exosomes taken from the mesenchymal stem cells could eventually be used to treat spinal cord injury. Those special exosomes would magnify the nerve cell-creating effect, perhaps restoring nerve cell function to a damaged spinal cord. Considerable research needs to be done before this possibility becomes a clinical reality, but this knowledge helps researchers design targeted experiments in the future.
A couple of weeks ago, scientists published findings showing that implanting human stem cells that are embedded within the engineered tissue can lead to the recovery of sensory perception in rats. The recovery of sensory perception is also accompanied by healing within the spinal cord and the ability to walk independently. The stem cells used in this experiment were collected from the membrane lining the mouth.
These results help demonstrate the potential for stem cells to help with spinal cord injuries but also point to the utility of combining stem cells with other factors to enhance their therapeutic effects. In this case, the researchers used a 3-dimensional scaffold to enable stem cells to attach and to stabilize them in the spinal cord. By adding growth factors, such as human thrombin and fibrinogen to the engineered tissue scaffolding, the researchers also increased the chances that attached stem cells would grow and differentiate.
The researchers compared the effects of their stem cell implants in paraplegic rats with the effects of adding no stem cells. Whereas the control rats who did not receive stem cells did not experience any improvement in mobility or sensation, 42% of the rats that did receive stem cells became better at supporting their weight on their hind limbs and at walking.
While these results are pre-clinical and do not apply directly to humans, the researchers conclude that further research is warranted. Given the positive impact of stem cells on the spinal cord in animals, it is reasonable to assume that stem cells may also benefit the human spinal cord. Further research will help clarify whether these stem cells can be adequately used to help treat patients with paraplegia.
For years, medical experts have warned of the medical concerns associated with opioids, including depression, weakened immune system, and digestive issues. Now, however, new research shows that they could be particularly dangerous for dementia patients.
The Dangers of Painkillers for Dementia Patients
According to research presented at the Alzheimer’s Association International Conference, opioid-based painkillers can triple the side effects of dementia. Individuals taking the drugs experienced more pronounced personality changes, significant increases in confusion and sedation, and lower activity levels throughout the day.
In another study, researchers focused exclusively on known as “Z drugs,” which are currently given to hundreds of thousands of patients with dementia to promote sleep. Drugs under this category included zolpidem, zopiclone, and zaleplon. Findings revealed that patients on these drugs faced an increased risk of bone fracture, which contributes to an increased risk of death in people with dementia.
A Widespread Problem
Alzheimer’s, which is the most common form of dementia, currently affects an estimated 5.7 million Americans. Roughly half of the people living in care homes and suffering from this or another form of dementia experience pain to some degree, which can result from unrelated medical conditions such as arthritis. Unfortunately, as dementia patients face compounding communication challenges, treating their pain can become more difficult.
The study has prompted experts to explore other, non-pharmaceutical means of treating pain and sleep disorders in dementia patients. Alzheimer’s research group leaders believe that the solution lies in finding nondrug interventions to help manage pain and promote quality of life while minimizing serious side effects like those revealed by the study findings. Regenerative therapy may be an option to consider for those battling Alzheimer’s disease or dementia.
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.