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fibroblasts

Diabetic foot ulcers: cell types identified that may contribute to healing

Diabetic foot ulcerations — open sores or wounds that refuse to heal – affect more than 15 percent of people with diabetes and result in thousands of lower extremity amputations per year in the United States.

To gain a better understanding of diabetic foot ulcers’ biology, a team of researchers at Emory and Beth Israel Deaconess Medical Center in Boston compared cells taken from patients with ulcers that healed to those taken from patients whose ulcers failed to heal, as well as to cells taken from intact forearm skin in patients with and without diabetes.

The team identified a subpopulation of fibroblasts enriched in the foot ulcers that healed, pointing to potential interventions. The results were published in Nature Communications on January 10.

“In this study, we present a comprehensive single cell map of the diabetic foot ulcer microenvironment,” says Manoj Bhasin, PhD, associate professor of pediatrics and biomedical informatics at Emory University School of Medicine, who is co-corresponding author of the study. “To our knowledge, we are the first to identify a unique subpopulation of fibroblasts that are significantly enriched in diabetic foot ulcers that are destined to heal.”

Various cell types, including endothelial cells, fibroblasts, keratinocytes and immune cells, were known to play an important role in wound healing processes. Yet diabetic foot ulcerations’ failure to heal and high associated mortality remain poorly understood.

“Our data suggests that specific fibroblast subtypes are key players in healing these ulcers and targeting these cells could be one therapeutic option,” says co-corresponding author Aristidis Veves, DSc, MD, director of the Rongxiang Xu, MD, Center for Regenerative Therapeutics and research director of the Joslin-Beth Israel Deaconess Foot Center. “While further testing is needed, our data set will be a valuable resource for diabetes, dermatology and wound healing research and can serve as the baseline for designing experiments for the assessment of therapeutic interventions.”

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Posted on by Quinn Eastman in Uncategorized Leave a comment

Direct reprogramming into endothelial cells

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 a way, this approach follows in Nobel Prize winner Shinya Yamanaka’s footsteps, but it also tunnels under the mountain he climbed. Direct reprogramming has been achieved for target cell types such as neurons and insulin-producing beta cells.

Young-sup Yoon, MD, PhD

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.

In contrast, Yoon’s team is able to produce cells that already have endothelial character hammered into them. The authors have applied for a patent. The co-first authors were instructor Sang-Ho Lee, PhD and Changwon Park, PhD, assistant professor of pediatrics. Read more

Posted on by Quinn Eastman in Heart Leave a comment