Stem cell researchers at Emory University School of Medicine have made an advance toward having a long-lasting “repair caulk” for blood vessels. The research could form the basis of a treatment for peripheral artery disease, derived from a patient’s own cells. Their results were recently published in the journal Circulation.
A team led by Young-sup Yoon, MD, PhD developed a new method for generating endothelial cells, which make up the lining of blood vessels, from human induced pluripotent stem cells.. When endothelial cells are surrounded by a supportive gel and implanted into mice with damaged blood vessels, they become part of the animals’ blood vessels, surviving for more than 10 months.
“We tried several different gels before finding the best one,” Yoon says. “This is the part that is my dream come true: the endothelial cells are really contributing to endogenous vessels. When I’ve shown these results to people in the field, they say ‘Wow.'”
Previous attempts to achieve the same effect elsewhere had implanted cells lasting only a few days to weeks, although those studies mostly used adult stem cells, such as mesenchymal stem cells or endothelial progenitor cells, he says.
“When cells are implanted on their own, many of them die quickly, and the main therapeutic benefits are from growth factors they secrete,” he adds. “When these endothelial cells are delivered in a gel, they are protected. It takes several weeks for most of them to migrate to vessels and incorporate into them.” Read more
Are there more cases of a given disease because something is causing more, or because doctors have become more aware of that disease? A recent paper in JAMA tackles this question for sepsis, the often deadly response to infection that is the most expensive condition treated in US hospitals.
Researchers from several academic medical centers, including Emory, teamed up to analyze sepsis cases using two methods. The first is based on the ICD (International Classification of Diseases) codes recorded for the patient’s stay in the hospital, which the authors refer to as “claims-based.” The second mines electronic medical record (EHR) data, monitoring the procedures and tests physicians used when treating a patient. The first approach is easier, but might be affected by changing diagnosis and coding practices, while the second is not possible at every hospital.
“This project was undertaken by several large, high quality institutions that have the ability to well characterize their sepsis patients and connect their EHR data,” says Greg Martin, MD, who is a co-author of the JAMA paper along with David Murphy, MD, PhD. The lead author, Chanu Rhee, MD, MPH, is from Brigham and Women’s Hospital, and the entire project was part of a Prevention Epicenter program sponsored by the Centers for Disease Control and Prevention. Read more
A paper from Emory investigators, published in AJOB Empirical Bioethics, touches on related current issues. The paper examines how race and close experience with traumatic brain injury affect study participants’ views of informed consent in clinical research.
This emerged from a study of community consultation for EFIC (exception from informed consent), in connection with a nationwide clinical trial of progesterone for traumatic brain injury (TBI). EFIC describes clinical research performed when the normal process of obtaining patients’ informed consent is not possible, because of emergency conditions such as seizures or TBI. Before such studies can be undertaken, the FDA calls for protective procedures and community consultation.
In this case, researchers surveyed 2612 people at 12 sites involved in the TBI study. The survey asked about attitudes toward the EFIC aspects of the study and also asked if they had personal experience with traumatic brain injury – either themselves or someone close to them. How that personal connection affected their responses was influenced by race.
Key paragraph from discussion:
Among white participants, increased levels of acceptance of EFIC were found among those with any connections to TBI. On the other hand, among participants identifying as black or other nonwhite races, there was decreased acceptance of EFIC enrollment among TBI patients and no increase in acceptance among those with a family member/loved one with TBI. The fact that black and white participants with no personal TBI experience or with a more distant connection to TBI had similar acceptance rates suggests that baseline acceptance of EFIC among these two groups is fairly similar and that the experience with the condition itself plays a role in driving the observed differences…
When facing a life-threatening infection, the “yuck factor” is a minor concern. Fecal microbiota transplant (FMT for short) has become an accepted treatment for recurrent Clostridium difficile infection, which can cause severe diarrhea and intestinal inflammation.
In a new video, Emory physicians Colleen Kraft and Tanvi Dhere explain how FMT restores microbial balance when someone’s internal garden has been disrupted.
C. difficile or “C diff” is a hardy bacterium that can barge into the intestines after another infection has been treated with antibiotics, when competition for real estate is low. In the last few years, doctors around the world have shown that FMT can resolve recurrent C diff infection better than antibiotics alone.
At Emory, Kraft and Dhere have performed almost 300 FMTs and report a 95 percent success rate when treating recurrent C diff. They have established a standard slate of stool donors, whose health is carefully screened.
Building on their experience with the procedure, Kraft and Dhere are studying whether FMT can head off other antibiotic-resistant infections besides C diff in kidney transplant patients. They have teamed up with infectious disease specialists Aneesh Mehta and Rachel Friedman-Moraco to conduct this study. Read more
A new paper in PNAS from Emory scientists highlights a neat example of bacterial evolution and adaptation related to sexually transmitted infections. Neisseria meningitidis, a bacterium usually associated with meningitis and sepsis, sometimes appears in the news because of cases on college campuses or other outbreaks.
Genetic changes make this clade look more like relatives that are known to cause gonorrhea. Some good news is that these guys are less likely to cause meningitis because they have lost their outer capsule. They have also gained enzymes that help them live in low oxygen.
The DNA analysis helps doctors track the spread of this type of bacteria and anticipate which vaccines might be protective against it. Thankfully, no alarming antibiotic resistance markers are present (yet) and currently available vaccines may be helpful. Full press release here, and information about meningococcal disease from the CDC here.
This looks like a well-worn path in bacterial evolution, since N. gonorrhoeae is thought to have evolved from N. meningitidis and there are recent independent examples of N. meningitidis adapting to the urogenital environment.
Lab Land went looking off the beaten path for individual stories of Emory cardiologists saving lives and was pleased to find several. We highlight here three remarkable case reports that are being presented at the ACC meeting. We look forward to learning more about these cases.
Electrical storm is life threatening and refers to a recurrent arrhythmia. The arrhythmia did not respond to drug treatment, so anesthesiologists were brought in to perform left stellate ganglion block, an injection of medication into a nerve bundle in the neck, allowing diagnosis and further treatment. It turns out the arrhythmia was caused by sarcoidosis, a rare intrusion of immune cells into the heart. [Saturday morning: Michael Lloyd, Boris Spektor]
A 30-year old woman came to doctors with drastically impaired heart function, although she did not have a blockage of her coronary arteries or signs of damage to the heart muscle. Doctors discovered a tumor near her spine that was producing heart-distorting hormones such as epinephrine. She underwent surgery to remove the tumor. [Saturday afternoon: Stamatios Lerakis]
Ten days after giving birth, a woman came to a hospital with chest pain. Upon cardiac catheterization, a rearrangement of her coronary arteries was discovered. It appears that the congenital defect had gone undetected until the stress of giving birth. Under medical treatment, she is asymptomatic, but she will need future monitoring and possibly a procedure to correct the artery problems. [Sunday morning: Camden Hebson]
Direct reprogramming has become a trend in the regenerative medicine field. It means taking readily available cells, such as skin cells or blood cells, and converting them into cells that researchers want for therapeutic purposes, skipping the stem cell stage.
In Circulation Research, Emory stem cell biologist Young-sup Yoon, MD, PhD and colleagues recently reported converting human skin fibroblast cells into endothelial cells, which line and maintain the health of blood vessels.
Once reprogrammed, a patient’s own cells could potentially be used to treat conditions such as peripheral artery disease, or to form vascular grafts. Exactly how reprogrammed cells should be deployed clinically still needs to be worked out.
In cardiovascular disease, many clinical trials have been performed using bone marrow cells that were not reprogrammed. Emory readers may be familiar with studies conducted by Arshed Quyyumi, MD and colleagues, in which treatment was delivered after patients’ heart attacks. In those studies, sorted progenitor cells, some of which could become endothelial cells, were introduced into the heart. To provide the observed effects, the introduced cells were more likely supplying supportive growth factors.
Basic research presentations at 2016 American Heart Association Scientific Sessions: cell therapy for heart attack (mesenchymal stem cells) in animal models and role of CD73, gradual release drug for atrial fibrillation, how particles from stored blood affects blood vessels.
Nov.13, 1:30 pm, Science and Technology Hall- Basic Science Theater
Cell therapy, using the patient’s own cells to reduce damage to the heart after a heart attack, has been a hot topic. Mesenchymal stem cells are derived from the bone marrow and can’t replace heart muscle. But they do exert anti-inflammatory and anti-oxidative effects, Eric Shin, MD, Rebecca Levit, MD and colleagues show in a rat model of heart attack.
The researchers use the gel material alginate to encapsulate the cells, in a way previously described by Levit. They say this is the first study to demonstrate that mesenchymal stem cells reduce reactive oxygen species production in the heart. and that the molecule CD73, which degrades ATP/ADP into adenosine, is needed for the anti-inflammatory effect. CD73 is also a cancer immunotherapy target. Read more
If you’ve been following the news about antibiotic resistant bacteria, you may have heard about a particularly alarming plasmid: MCR-1. A plasmid is a circle of DNA that is relatively small and mobile – an easy way for genetic information to spread between bacteria. MCR-1 raises concern because it provides bacteria resistance against the last-resort antibiotic colistin. The CDC reports MCR-1 was found in both patients and livestock in the United States this summer.
This suggests that the pressure of fighting the host immune system may select for MCR-1 to stick around, even in the absence of colistin use, the authors say.
While the findings are straightforward in bacterial culture, Weiss cautions that there is not yet evidence showing that this mechanism occurs in live hosts. For those that really want to get alarmed, he also calls attention to a recent Nature Microbiology paper describing a hybrid plasmid with both MCR-1 and resistance to carbapenem, another antibiotic.
Lots of people in the United States consume a diet that is high in sugar and fat, and many develop non-alcoholic fatty liver disease, a relatively innocuous condition. NASH (non-alcoholic steatohepatitis) is the more unruly version, linked to elevated risk of cardiovascular and metabolic diseases, and can progress to cirrhosis. NASH is expected to become the leading indication for liver transplant. But only a fraction of people with non-alcoholic fatty liver disease go on to develop NASH.
Thus, many researchers are trying to solve this equation:
High-sugar, high-fat diet plus X results in NASH.
Emory hepatologist Frank Anania and colleagues make the case in a recent Gastroenterology paper that a “leaky gut”, allowing intestinal microbes to promote liver inflammation, could be a missing X factor.
Anania’s lab started off with mice fed a diet high in saturated fat, fructose and cholesterol (in the figure, HFCD). This combination gives the mice moderate fatty liver disease and metabolic syndrome (see this 2015 paper, and we can expect to hear more about this model soon from Saul Karpen). Leaky gut, brought about by removing a junction protein from intestinal cells, sped up and intensified the development of NASH.
The authors say that this model could be useful for the study of NASH, which has been difficult to reproduce in mice.