News Release

Philadelphia—A cure for type-1 diabetes has come closer with the development of a new method for keeping transplanted insulin-producing cells alive and functional in recipients for long periods even when transplanted underneath the skin. A team led by researchers at the Perelman School of Medicine at the University of Pennsylvania reports the new method, and its successful testing in multiple animal models, in a paper that published in Nature Metabolism.

Type 1 diabetes, which affects more than 1.25 million people in the United States, usually strikes in childhood and is caused by an abnormal immune reaction. The immune reaction attacks and destroys cells in the pancreas known as beta cells—specialized cells that cluster in groupings called “islets” and help regulate blood sugar levels by producing insulin.

Transplantation of healthy islets of beta cells from donors has long been viewed as a potential cure for the condition, which otherwise requires life-long frequent insulin injections and blood-sugar monitoring. But researchers have had difficulty keeping transplanted beta cells alive for the long-term. The new method appears largely to overcome this difficulty, as shown in a variety of subcutaneous beta-cell transplants to mice and monkeys. These preclinical demonstrations could pave the way for clinical trials in human patients.

“Transplanting beta cells under the skin of patients may have many advantages, including safety and ease of monitoring, and here, we’ve shown in preclinical experiments that these grafted cells can survive and function to reverse diabetes long-term,” said study senior author Ali Naji, MD, PhD, the J. William White Professor of Surgical Research at Penn.

The most widely used technique for transplanting beta cells is to infuse them into the portal vein of the liver. However, this procedure has many shortcomings, including the early loss of islets and potential complications associated with it, such as bleeding and thromboses.

Injecting beta cells under the skin is, in principle, an easier and safer technique. In practice, though, donor beta cells have tended to die even more quickly in the subcutaneous environment, in part because they fail to induce the formation of new blood vessels to supply them with oxygen and nutrients.

To address this challenge, Naji’s team developed a mixture of molecules, including collagen, a protein found in skin and cartilage, that partly recreate the molecular environment of the pancreas where beta cells normally grow. Islet Viability Matrix (IVM), as they call this mix, also seems to specifically promote the survival of beta cells in conditions where they would otherwise perish.

“IVM appears to suppress signaling that normally would trigger cell death, and, at the same time, appears to promote the formation of new blood vessels that can supply the cells with nutrients,” said co-corresponding and co-lead author Divyansh Agarwal, PhD, a surgeon-scientist in-training and an MD/PhD student in his final year of the combined degree program at Penn.

Testing IVM and beta cell transplantation in a standard diabetic mouse model, the researchers found that IVM made all the difference: beta cells implanted without IVM simply failed to function, whereas beta cells implanted with IVM brought the mice’s blood sugar levels under control within a day—and kept doing so until the mice were sacrificed months later for analysis of the grafted cells.

The team showed that they could get similar results, using IVM, whether they were transplanting the mice’s own beta cells, or beta cells from humans or pigs. Initial experiments were in mice lacking an immune system, but the team obtained essentially the same results when they used “immune competent” mice and, to prevent transplant rejection, dosed the animals with immune-suppressing drugs that transplant recipients normally take.

Lastly, work led by Chengyang Liu, MD, an adjunct professor of Surgery in Naji’s laboratory, showed that with IVM, subcutaneously injected beta cells survived and provided blood sugar control for more than two years in a macaque monkey.

Beta cells transplanted into people with type 1 diabetes normally come from other human donors, which means that the recipients need to take immunosuppressive drugs indefinitely to prevent the immune rejection of the “foreign” cells. However, Naji and his colleagues now plan to team up with study co-author Bernhard Hering, MD, a professor in the Department of Surgery at the University of Minnesota, who has developed a method to induce immune tolerance of donor cells—a method that may reduce or eliminate the need for chronic immunosuppression.

“Combining IVM-based subcutaneous transplant with Bernhard’s immune tolerance technique could be a very powerful combination, and we look forward to testing this method further,” Naji said.

The other co-authors of the study were Ming Yu, Laxminarayana Korutla, Catherine May, Wei Wang, and Klaus Kaestner, all of Penn Medicine; and Negin Noorchashm Griffith, Omaida Velazquez, James Markmann, and Prashanth Vallabhajosyula, from other institutions. The researchers were funded by the National Institutes of Health (NIH/NIDDK DK070430, NIH/NIAID AI-102430 and NIH/NIDDK UC4–112217).         


Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.

The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.

Share This Page: