Scientists at the Wake Forest Institute for Regenerative Medicine (WFIRM) have developed the world’s most sophisticated laboratory model of the human body, creating a system of miniaturized organs that can be used to detect harmful and adverse effects of drugs before they are prescribed to patients.
Using such a system in screening potential pharmaceuticals could have a significant impact on speeding new drugs to market, lowering the cost of clinical trials, and reducing or eliminating animal testing.
The system, developed from funding provided by the Defense Threat Reduction Agency, is built from many human cell types that are combined into human tissues representing a majority of the organs in the human body such as the heart, liver and lungs. Each of these miniature organs are tiny 3D tissue-like structures about one millionth the size of an adult human organ. The system can be used to mimic tissues/organs and can be used as a testing and predicting platform.
“The most important capability of the human organ tissue system is the ability to determine whether or not a drug is toxic to humans very early in development, and its potential use in personalized medicine,” said Anthony Atala, MD, WFIRM director and senior author of the study, which was published in the journal Biofabrication. “Weeding out problematic drugs early in the development or therapy process can literally save billions of dollars and potentially save lives.”
To understand why men are at greater risk than women for more severe symptoms and worse outcomes from COVID-19 regardless of age, scientists at the School of Medicine conducted a review of published preclinical data on sex-specific hormone activity, especially estrogen. The review was published in the September online issue of the journal Current Hypertension Reports.
“We know that coronavirus affects the heart and we know that estrogen is protective against cardiovascular disease in women, so the most likely explanation seemed to be hormonal differences between the sexes,” said the lead author of the review, Leanne Groban, MD, House Staff ’98, professor of anesthesiology.
Groban’s researchers said the published literature indicated that the angiotensin-converting enzyme2 (ACE2), which is attached to cell membranes in the heart, arteries, kidneys and intestines, is the cellular receptor of the coronavirus responsible for COVID-19 infections, and helps bring the virus into the cells of those organ systems.
The review, they said, also pointed to estrogen’s lowering the level of ACE2 in the heart, which may modulate the severity of COVID-19 in women. Conversely, higher levels of ACE2 in tissues could account for why symptoms are worse in men than women, Groban said.
Among people who have the most common type of lung cancer, up to 40% develop metastatic brain tumors, with an average survival time of less than six months, but why non-small-cell lung cancer so often spreads to the brain has been poorly understood.
School of Medicine scientists have found that nicotine, a non-carcinogenic chemical found in tobacco, actually promotes the spread of lung cancer cells into the brain.
“Based on our findings, we don’t think that nicotine replacement products are the safest way for people with lung cancer to stop smoking,” said Kounosuke Watabe, PhD, professor of cancer biology and lead author of the study, published in June in the Journal of Experimental Medicine.
Watabe and colleagues looked for drugs that might reverse the effects of nicotine and identified parthenolide, a naturally occurring substance in the medicinal herb feverfew, which blocked nicotine-induced brain metastasis in mice. Because feverfew is considered safe, Watabe believes parthenolide may provide a new approach to fight brain metastasis, particularly for patients who have smoked or still smoke.
More than 90% of the legal marijuana products offered in medical dispensaries are much stronger than what clinical studies have shown that doctors recommend for chronic pain relief, according to a study published online in March in the journal PLOS ONE.
“We know that high-potency products should not have a place in the medical realm because of the high risk of developing cannabis-use disorders, which are related to exposure to high THC-content products,” said the study’s lead author, E. Alfonso Romero-Sandoval, MD, PhD, associate professor of anesthesiology.
Romero-Sandoval’s team found that most of the products offered in the medical dispensaries in the study had more than 10% tetrahydrocannabinol (THC), the compound that provides pain relief as well as intoxication, and that many had 15% or more, the same as what is available in products at recreational dispensaries. Previous studies have shown that levels of up to 5% THC were sufficient to reduce chronic pain with minimal side effects.
Between 60% and 80% of people who use medical marijuana use it for pain relief, Romero-Sandoval said. The higher the concentration of THC, the greater the risk for developing dependency and for developing tolerance more quickly, which means higher and higher concentrations might be needed to get the same level of pain relief.
Research reported in this publication was supported by the following sources and grants from the National Institutes of Health (NIH):
Estrogen May Lessen Severity of COVID-19 Symptoms in Women: Program project grant HL-051952 from the National Heart, Lung and Blood Institute and grants AG042758 and AG033727 from the National Institute on Aging.
Scientists Discover that Nicotine Promotes Spread of Lung Cancer to the Brain: NIH grants RO1CA173499, R01CA185650 and R01CA205067 (to K. Watabe). This research used Cancer Center Shared Resources, the Tumor Tissue and Pathology, Cell Engineering, Flow Cytometry, Biostatistics and Bioinformatics that are supported by the Comprehensive Cancer Center of the Wake Forest University National Cancer Institute, National Institutes of Health grant P30CA012197.
Study Shows Legal Marijuana Products Too Strong for Pain Relief: Department of Anesthesiology, Wake Forest Baptist Health.