'Super-grafts' that could treat diabetes

November 06, 2019

To save patients with a severe form of type 1 diabetes (characterized by the absence of functional insulin-producing cells), pancreatic cell transplantation is sometimes the last resort. The pancreas contains cell clusters - called islets of Langerhans - where cells that produce blood glucose regulating hormones are grouped together. However, the transplant process is long and complex: a significant part of the grafted cells die quickly without being able to engraft. By adding amniotic epithelial cells to these cell clusters, researchers at the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG), Switzerland, have succeeded in creating much more robust "super-islets" of Langerhans. Once transplanted, more of them engraft; they then start producing insulin much more rapidly. These results, to be discovered in Nature Communications, would not only improve the success of cell transplants, but also offer new perspectives for other types of transplants, including stem cell transplantation.

Today, islet transplantation is one of the last-chance options for patients with a particularly severe form of type 1 diabetes. The islets are removed from a donor's pancreas, isolated and then re-injected into the patient's liver. "The procedure is well controlled - about fifteen patients benefit from it every year in Switzerland - but nevertheless complex, says Ekaterine Berishvili, a researcher in the Department of Surgery at UNIGE Faculty of Medicine, who led this work. Many of the islets die along the way. It often takes several donors to treat one person, whereas we are in desperate need of donors."

Placental cells to help grafts

To improve the success of islet transplantation and the survival of transplanted cells, researchers in Geneva have sought to create new, more robust islets that would withstand the stress of transplantation better than natural islets. To do this, they came up with the idea of adding amniotic epithelial cells, taken from the wall of the inner placenta membrane, to the pancreatic cells. "These cells, very similar to stem cells, are already used in other therapies, such as corneal repair for example," says Thierry Berney, Professor in the Department of Surgery at UNIGE Faculty of Medicine and Head of HUG Transplant Division, who co-directed this work. "In our case, we found that they can promote the function of pancreatic cells, which is to produce hormones according to fluctuations in sugar levels."

First step, in vitro: the addition of amniotic epithelial cells allowed the cell clusters to form regular spheres, indicating better intracellular communication and connectivity. Second step in vivo: the scientists transplanted their "super-islets" of Langerhans into diabetic mice, which quickly began to produce insulin. "Even with few cell clusters, our super islets adapted very well to their new environment and quickly became vascularized," says Fanny Lebreton, a researcher in the Department of Surgery at UNIGE Faculty of Medicine and the first author of this work. A good vascularization is indeed the key element of any transplantation: it allows to supply the new organ with oxygen and nutrients and guarantees their survival. In addition, the artificial islets quickly began to produce insulin.

Improving oxygenation and protecting islets

Amniotic epithelial cells are thus essential to islet survival and seem to act on two vital elements: the lack of oxygen, which usually kills a large number of transplanted islets, and the modulation of the host immune system to limit the risk of rejection. "In any transplant, the first step is to lower the recipient's immunity to limit the risk of rejection, says Ekaterine Berishvili. Amniotic epithelial cells have the unique characteristic of protecting the foetus, which is also a "non-self," from attacks by its mother's immune system. We believe that the same mechanism is at work to protect the grafts." The protective mechanism, observed here on cell transplants, could also take place in other types of transplants or even in xenotransplantation - where non-human cells or organs are transplanted into humans.

These discoveries now need to be confirmed on human subjects. Since the use of amniotic epithelial cells is already common in other clinical settings without adverse side effects, this could be done relatively quickly. An important hope for all those awaiting a transplant.
-end-
This work was supported by the Swiss National Science Foundation, the Fondation Privée des HUG, the Fondation Romande de Recherche sur le Diabète and the European Foundation for the Study of Diabetes, as well as by the Juvenile Diabetes Research Foundation.

Université de Genève

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.