An experimental strategy in Type 1 diabetes treatment, based on regenerative medicine, is called pancreatic islet transplantation.
In this strategy, islet cells (the cells responsible for the production of insulin) from a donor pancreas are transplanted into a person with Type 1 diabetes.
Because the beta cells in islets are selectively destroyed by an autoimmune process in those with Type 1 diabetes, islet transplantation can restore the physiological function in patients with this type of diabetes.
However, the technique isn’t without challenges.
The first cause of the loss of functionality in transplanted pancreatic islets is the low capacity to create new vessels to allow the arrival of nutrients in the cells. This is one of the main reasons causing the failure in transplantations in the treatment of Type 1 diabetes.
Ramon Gomis, professor at the Faculty of Medicine and Health Sciences of the University of Barcelona, head of the IDIBAPS research group Pancreatic Islets and Rosa Gasa, and their team decided to understand more.
They led a study that identifies a protein as a potential modulator in the revascularization of pancreatic islets.
In a study conducted on diabetic mice with islet transplant from other animals or human islets, researchers showed that grafts without this protein have higher revascularization -favoring the viability of cells- and regular sugar levels and glucose tolerance are recovered.
In the context of islet transplantation, there are two basic challenges to face and which are related to the chronic administration of immunosupressants and the fact that the transplant is not re-vascularized properly, which makes it harder for the nutrients and oxygen to arrive.
This deficiency causes the islets to stop being viable and to die.
Gomis says the regular environment for islets is formed by a heavy network of capillaries in charge of the arrival of oxygen, hormones and nutrients and the transport of the generated hormones to the blood vessel.
During the transplant process, islets are separated from their vascular network and their function and survival depend on the ability to create new vessels for the vascular system in the receptor.
“Islet implantation is revascularized, but not fast enough,” notes Gasa, “In our research, we focused on getting enough vessels to keep the islets in optimal conditions and improve the success of this strategy for the treatment of Type 1 diabetes.”
Improving revascularization: One of the challenges
In the study, researchers identified a molecular target -PTP1B phosphatase- which would allow transplanted pancreatic islets to be viable.
The results show the inhibition of this enzyme -present in all cells including pancreatic beta cells- promotes the activity of the pro-angiogenic growth factor VEGF, which enables the creation of new blood vessels.
Therefore, it gives a higher re-vascularization of the treatment that improves islet survival and functionality.
“Regulation of the re-vascularization is induced by hypoxia the lack of nutrients and the inhibition of phosphatase widens this response,” says Gasa. “When the stimuli disappear, the creation of new blood vessels stops.”
The researchers say their research is concept proof that can remove one of the reasons why the pancreatic islet transplant fails.
There are less specific inhibitors of PTP1B and phosphatases and therefore, the next step will be to test these inhibitors in the islet transplant in humans and assess its success, concludes Gomis.
Feature image: The inhibition of the PTP1B phosphatase activity makes the transplanted beta cells in the pancreas to survive and fulfill their function, with which the regular sugar levels can be recovered. Credit: Figueiredo et al.
The research has been published in Science Translational Medicine.
The University of Barcelona.
- The University of Barcelona. (2019, June 20). Researchers find a mechanism to improve pancreatic islet transplantation in Type 1 diabetes. EurekAlert! Retrieved June 21, 2019, https://www.eurekalert.org/pub_releases/2019-06/uob-rfa062019.php