Wake Forest Institute for Regenerative Medicine (WFIRM) scientists are working on a promising approach for treating chronic kidney disease—regeneration of damaged tissues using therapeutic cells.
By harnessing the unique properties of human amniotic fluid-derived stem cells, WFIRM scientists have demonstrated that the cells could potentially help recover organ function in a pre-clinical model of kidney disease.
“Our results indicate that this type of stem cell could be used as an off-the-shelf universal cell source and may provide an alternative therapeutic strategy for patients suffering from this chronic and debilitating disease,” said senior author James J. Yoo, MD, PhD, professor of regenerative medicine.
Study results were published online in the journal Tissue Engineering Part A.
Researchers found that amniotic fluid stem cells injected into a diseased kidney in a pre-clinical model led to improved kidney function by reducing damage to a group of capillaries that filters waste products from the blood.
Known worldwide for their pioneering research on 3-D bioprinting of tissues and organs, WFIRM researchers have also been tackling kidney disease and the shortage of organs in a variety of ways.
Kidney disease is a global public health problem that can manifest in acute and chronic symptoms. More than 30 million American adults are affected by the disease, and millions more are at risk of developing it, according to the National Kidney Foundation.
Facial wounds or burns could one day be treated with skin tissue regenerated with the use of a 3-D bioprinted BioMask created by Wake Forest Institute for Regenerative Medicine (WFIRM) scientists.
Skin injury or burns to the face are difficult to treat due to the varied contours and complex movement of the muscles. Current strategies to treat extensive facial wounds and burns
are limited to the use of skin grafts and skin substitutes which can often lead to scarring, infection or graft failure.
In recent decades, regenerative medicine and tissue engineering has emerged as an effective method for skin regeneration. Bioengineered skin substitutes can be created from both natural and synthetic materials and are most commonly placed directly on the skin wound site, but they are limited in size and some require a lengthy preparation time. And, with traditional skin grafts, many burn patients do not have enough unburned skin to harvest grafts.
The BioMask could change that. This proof-of-concept study, published online in the journal Bioprinting, involved the novel strategy of a customized, bioengineered skin substitute combined with a wound dressing layer to snugly fit onto a facial wound to regenerate skin.
“For patients who suffer from disfiguring facial wounds, the BioMask could one day be used as an effective treatment that would greatly improve their quality of life,” said lead author Sang Jin Lee, PhD, associate professor of regenerative medicine.
Wake Forest Baptist Health scientists have been awarded $3.9 million from the National Institutes of Health to determine if a procedure used to treat Parkinson’s patients can improve age-related cognitive abilities and counteract the effects of Alzheimer’s and other types of dementia.
Under the five-year grant, which will be conducted in collaboration with the Medical College of Georgia, the researchers will study deep brain stimulation (DBS) in an animal model. The study is designed to test the effectiveness of DBS in improving memory and evaluate the duration of benefits after the intervention.
“Based on our previous research, we anticipate that deep brain stimulation will improve cognitive performance, but we also hope that it will prove to be an effective intervention for Alzheimer’s,” said the study’s principal investigator Christos Constantinidis, PhD, professor of neurobiology and anatomy.
The study is being conducted in nonhuman primates because they experience age-related cognitive decline similar to humans and develop amyloid deposits in old age, a hallmark of Alzheimer’s in humans.
Alzheimer’s research is a priority area of NIA due to the annual cost for care of Alzheimer’s patients in the United States exceeding $277 billion or $850 for each U.S. resident.
Intensive control of blood pressure in older people significantly reduced the risk of developing mild cognitive impairment (MCI), a precursor of early dementia, in a clinical trial led by scientists at Wake Forest Baptist Health.
However, the National Institutes of Health-supported Systolic Blood Pressure Intervention Trial (SPRINT) Memory and Cognition in Decreased Hypertension (SPRINT MIND) study did not prove that treating blood pressure to a goal of 120 mm Hg or less statistically reduced the risk of dementia. This result may have been due to too few new cases of dementia occurring in the study, the authors noted.
“As doctors treating older patients, we are encouraged to finally have a proven intervention to lower someone’s risk for MCI,” said the study’s principal investigator, Jeff Williamson, MD, professor of gerontology and geriatric medicine. “In the study, we found that just three years of lowering blood pressure not only dramatically helped the heart but also helped the brain.”
The results were reported in the Journal of the American Medical Association.
Bacteria that make up the gut microbiome may be the reason why orally administered drugs for diabetes work for some people but not others, according to Wake Forest Baptist Health researchers.
“For example, certain drugs work fine when given intravenously and go directly to the circulation, but when they are taken orally and pass through the gut, they don’t work,” said Hariom Yadav, PhD, assistant professor of molecular medicine. “Conversely, metformin, a commonly used anti-diabetes drug, works best when given orally but does not work when given through IV.”
In a review of more than 100 current published studies in humans and rodents, the research team examined how gut bacteria either enhanced or inhibited a drug’s effectiveness.
The researchers determined that the metabolic capacity of a patient’s microbiome could influence the absorption and function of the diabetes drugs by making them pharmacologically active, inactive or even toxic.
They concluded that modulating the gut microbiome with drugs may represent a target to improve, modify or reverse the effectiveness of current medications for type-2 diabetes.
The review was published in the journal EBiomedicine.
Scientists at the Wake Forest Institute for Regenerative Medicine (WFIRM) have developed a process that could change the way cancer of the appendix is treated.
WFIRM researchers worked with colleagues from surgical oncology at Wake Forest Baptist Health to create a patient-specific tumor organoid model to identify the most effective treatment for each tumor. Organoids are miniaturized and simplified versions of an organ that are derived from stem cells.
Appendix cancer is rare, affecting only 1 in 100,000 people, and every patient responds differently to the many chemotherapy treatments available.
“There’s a variable response to the same sets of drugs across patients, so they do typically respond to a drug. We just need the right one,” said Aleksander Skardal, PhD, associate professor of regenerative medicine who was lead investigator along with Konstantinos Votanopoulos, MD, PhD.
Researchers created tumor organoids successfully for nine out of 12 patients, an impressive result for an early stage investigation. The study suggests that the organoid model can accurately represent what occurs inside a patient’s body and may be useful in selecting the most effective chemotherapy treatment.
“Organoid technology can be a game-changer in cancer patient care,” Votanopoulos said. “The way cancer is treated has improved over the years, but in general, we are still treating patients based on statistics, and not based on individual signatures of their cancer. We now have the capability to test drug responses of a patient’s own tumor cells in the lab prior to administering chemotherapies, or even immunotherapies, clinically.”
Their results were published in the Annals of Surgical Oncology.
Although several drugs are used to treat multiple myeloma (MM), a research team at Wake Forest Baptist Health may have found an effective new drug.
Led by Mikhail A. Nikiforov, PhD, professor of cancer biology, the scientists reported in The Journal of Clinical Investigation that they identified a drug currently used to treat leprosy and tuberculosis as a potential new therapy for MM patients.
Through a review of a virtual drug database, Nikiforov’s team identified clofazimine as a potent aryl hydrocarbon receptor (AHR) inhibitor and a suppressor of polyamine production. The team found that, in an animal model, clofazimine was highly effective and comparable to bortezomib, a drug currently used to treat MM.
In a commentary published in the journal, Robert A. Casero Jr., PhD, of Johns Hopkins School of Medicine, characterized this new finding as “intriguing and provides promise for moving such a strategy to the clinic.”
MM is an incurable type of blood cancer that affects plasma cells in the bone. Approximately 100,000 Americans are believed to have the disease.
Research reported on in this publication was supported by the following grants from the National Institutes of Health (NIH):
Bioengineered BioMask Offers Hope for Healing Facial Skin Injuries: NIH grant 1P41EB023833-01.
NIH Grant to Fund Study of Deep Brain Stimulation for Alzheimer’s: National Institute of Aging grant 1R01AG060754-01A1.
Researchers Identify Novel Molecular Mechanism Involved in Alzheimer’s: NIH grants K99/R00 AG044469, R01 AG055581, R01 AG056622, F31AG055264, F31AG054113, P50AG005136, U01AG006781; also Alzheimer’s Association grant NIRG-15-362799, BrightFocus Foundation grant A2017457S, Wake Forest Alzheimer’s Disease Core Center pilot grant P30AG049638, Wake Forest Clinical and Translational Science Institute pilot grant, and the Nancy and Buster Alvord Endowment.
Lowering Blood Pressure Reduces Risk of Cognitive Impairment: NIH contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C, and interagency agreement A-HL-13-002-001; clinical trial number: NCT01206062.
First-ever Model Developed for Patient-specific Treatment of Appendix Cancer: A Wake Forest Clinical and Translational Science Institute Pilot Award (NIH UL1 TR001420); also internal funding from the Comprehensive Cancer Center at Wake Forest Baptist Health.
Anti-leprosy Drug Shows Promise as Multiple Myeloma Treatment: NIH grants CA220096, CA224434, CA193981 and CA190533; a Ruth L. Kirschstein National Research Service Award F32CA189622; NIH grants CA197996, 1F99CA21245501, R01AI100157 and R01CA121044; the Jennifer Linscott Tietgen Foundation; and in part by a National Cancer Institute Cancer Center Support Grant P30CA16056 to the Roswell Park Comprehensive Cancer Center, for the Clinical Data Network and the Animal Facility.