A groundbreaking study from Weill Cornell Medicine has unveiled a comprehensive map of endothelial cells that line blood vessels in the insulin-producing “islets” of the human pancreas, offering new insights into potential treatments for diabetes and other pancreatic diseases. These cells, known as islet-specific endothelial cells (ISECs), have long been difficult to study, but the new findings could serve as a crucial resource for advancing pancreatic research.
Published in Nature Communications on February 6, the study introduces a novel method for isolating and analyzing ISECs from donor pancreases, a task previously hindered by the cells’ rapid deterioration when removed using conventional techniques. The researchers successfully isolated and profiled thousands of these cells, unveiling their molecular characteristics and their interactions with other pancreatic cells.
“This dataset represents the first full spectrum of endothelial cells within the pancreas,” said David Redmond, Ph.D., assistant professor of computational biology at the Hartman Institute for Therapeutic Organ Regeneration at Weill Cornell Medicine. “It will be an invaluable resource for both our team and other researchers in the field.”
Redmond co-authored the study with Dr. Shahin Rafii, a distinguished professor of genetic medicine and director of both the Hartman Institute and the Ansary Stem Cell Institute at Weill Cornell Medicine. Together, they led a team that mapped out how ISECs contribute to the maturation, insulin production, and survival of pancreatic islet cells.
ISECs are also vital for the success of islet transplants, a treatment for Type 1 diabetes that remains limited due to immune rejection issues. The research opens doors to improving the longevity and function of these transplants, which could ultimately help address the challenges of curing diabetes.
The study, spearheaded by Dr. Rebecca Craig-Schapiro, an assistant professor of surgery and transplant surgeon at NewYork-Presbyterian/Weill Cornell Medical Center, involved analyzing pancreases from three deceased organ donors. Craig-Schapiro’s team isolated over 30,000 ISECs, along with 75,000 other pancreatic cells, preserving their viability long enough to conduct detailed single-cell RNA sequencing.
The RNA sequencing provided deep insights into gene expression profiles of ISECs and other pancreatic cells, allowing the researchers to map out the interactions between various cell types within the pancreas.
“We were able to identify the unique gene signatures of ISECs and pinpoint supporting cells that communicate with them,” said Kevin Chen, a research technician in the Rafii lab.
While the molecular features of ISECs were previously unknown, the study validated existing knowledge and expanded upon it. The researchers integrated their findings with data from other published studies, creating a more complete “cell atlas” of the pancreas.
With a focus on insulin production, pancreatic islets are critical for diabetes research. The new data could help pinpoint endothelial genes and signaling pathways disrupted in diabetes, providing targets for future therapeutic strategies.
“This atlas lays the groundwork for developing new therapies to restore the function of ISECs and other pancreatic cells,” said Dr. Rafii. “It also offers promising avenues for addressing pancreatic diseases beyond diabetes.”
Looking ahead, Rafii and his team are now applying their findings to develop methods for generating ISECs from other types of cells, offering further hope for innovative treatments. Dr. Rafii, also a member of Weill Cornell Medicine’s Englander Institute for Precision Medicine, has ties to Angiocrine Bioscience, a company focused on regenerative medicine.
This research was funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation, and other institutions dedicated to advancing medical innovation.
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