Unique pancreatic stem cells are the key to diabetes care

Scientists from the Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine have confirmed the existence of stem cells within the human pancreas that can be activated to produce glucose-responsive beta cells. The results, published on February 27, 2018 in Cell Reports, are of great importance for the development of regenerative cell therapy for the treatment of diabetics.

The theory that stem cells (precursor cells), potentially capable of restoring Langerhans islets, can be found in the pancreas, has been discussed for decades, but not conclusively demonstrated.

DRI scientists have now been able to determine the exact anatomical location of these stem cells and validate their proliferative potential and ability to turn into glucose-responsive beta cells.

“Our in-depth study of these pancreatic stem cells may help us tap into an endogenous cell supply ‘bank’ for beta cell regeneration purposes and, in the future, lead to therapeutic applications for people living with type 1 diabetes”, – said Juan Dominguez-Bendala, Ph.D., DRI director of pancreatic stem cell development for translational research and co-principal investigator of the study.

“Together with our previous findings using BMP-7 to stimulate their growth, we believe that we may be able to induce these stem cells to become functional islets.”

Previously, the DRI team reported that bone morphogenetic protein 7 (BMP-7), a natural growth factor already approved by the Food and Drug Administration (FDA) for clinical use, stimulates progenitor cells in cultured non-endocrine pancreatic tissue.

In a new study scientists went on to demonstrate that stem cells that react to BMP-7 reside within the pancreatic ductal and glandular network of the organ.

In addition, cells are characterized by the expression of PDX1, a protein necessary for the development of beta cells, and ALK3, a cell surface receptor associated with the regeneration of certain types of tissues.

Using “molecular fishing” methods, the researchers were able to selectively extract the cells expressing PDX1 and ALK3, cultivate them in the laboratory and show that they can proliferate in the presence of BMP-7, and then differentiate into beta cells. The results of the research will help scientists to approach the development of regenerative cell therapies for type 1, and potentially type 2, diabetes.

In type 1 diabetes, autoimmune lesion of beta cells occurs. This type of diabetes leads to a full lifelong dependence on insulin injections. The patient must constantly monitor the blood glucose level and adjust the insulin dosage on his own.

With type 2 diabetes, the ability of the pancreas to produce insulin is not completely lost. However, the body becomes more resistant to insulin. Consequently, if the body does not react to the normal level of insulin in the blood, then the pancreas has to produce more and more insulin. Without proper treatment, this leads to depletion of the pancreas, dysfunction of beta cells and absolute insulin deficiency.

The transplantation of the islets of Langerhans has allowed some patients with type 1 diabetes to live without mandatory insulin injections. However, donor cells are not enough to treat millions of diabetics.

Thus far, researchers have focused mainly on creating a large number of pancreatic cells for transplantation from sources such as embryonic (hESCs), pluripotent (hCPCs) and adult human stem cells, and porcine (pig) islets, among others.

The most effective and safe solution to the problem could lie in regenerating a patient’s own insulin-producing cells, bypassing the need to transplant donor tissue altogether and reducing other immune-related roadblocks.

“The ability to offer regenerative medicine strategies to restore insulin production in the native pancreas could one day replace the need for transplantation of the pancreas or insulin-producing cells.

In type 1 diabetes, this would require abrogation of autoimmunity to avoid immune destruction of the newly formed insulin producing cells. For this reason our current efforts are converging on immune tolerance induction without the need for life long anti-rejection drugs”, – said Camillo Ricordi, M.D., director of the Diabetes Research Institute.