HONG KONG – Scientists at the Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine have for the first time confirmed the existence of human pancreatic progenitor cells and have shown they can be induced to develop into glucose-responsive pancreatic beta cells.

Those findings, published in the Feb. 27, 2018, edition of Cell Reports, give rise to the opportunity for developing curative regenerative cell therapies for patients with type 1 diabetes and potentially those with type 2.

Affecting more than 420 million people worldwide, the annual global cost of diabetes was estimated at more than $825 billion in a 2016 study performed by Harvard University, Imperial College London and the WHO.

Previously known as juvenile diabetes, type 1 disease results when insulin-producing pancreatic beta cells have been destroyed by the immune system, requiring daily insulin to regulate glucose levels. Type 2 patients can produce some insulin, but the beta cells may become dysfunctional over time, requiring additional medications such as metformin.

"Insulin keeps type 1 diabetics alive, but exogenous insulin administration brings a host of complications down the line, including blindness, amputations and kidney failure," Juan Dominguez-Bendala, DRI director of pancreatic stem cell development for translational research, told BioWorld.

"We need therapies aimed at restoring the body's natural ability to control glucose homeostasis," said Dominguez-Bendala, the study's co-principal study author together with Ricardo Pastori, the DRI's director of molecular biology.

New therapies are needed not least because the incidence of both diabetes types is increasing. "Type 2 disease is on the rise owing to increased obesity and more sedentary lifestyles," noted Dominguez-Bendala.

"Type 1 diabetes is one of many autoimmune diseases in which we have also seen a very significant rise. The reasons for this are unclear, but growing evidence points at environmental triggers such as viral infections that, combined with genetic predisposition, may lead to disease."

However, despite that increased prevalence, a diabetes cure remains elusive.

That the pancreas might harbor progenitor cells that could regenerate insulin-producing islets has long been proposed, but never previously convincingly demonstrated.

Now the DRI scientists have identified the location of those stem cells and established their proliferative potential and ability to become glucose-responsive beta cells.

"Our study of these pancreatic stem cells may help us tap into an endogenous cell supply for beta cell regeneration and therapeutic applications for type 1 diabetes," said Dominguez-Bendala.

"Together with our previous findings using [bone morphogenic protein-7] BMP-7 to stimulate their growth, we believe that we may be able to induce these stem cells to become functional islets."

The DRI team had previously reported in Diabetes in 2015 that BMP-7, a naturally occurring bone growth factor already approved by the FDA for orthopedic use, stimulates progenitor-like cells within cultured human non-endocrine pancreatic tissue.

In their new study, the DRI researchers demonstrated that those stem cells that respond to BMP-7 reside within the pancreatic ductal and glandular network.

Additionally, the cells are characterized by expression of PDX1, also known as insulin promoting factor 1, a protein necessary for beta cell development, and ALK3, a cell surface receptor associated with regeneration of multiple tissues.

Using cell sorting techniques, the researchers used antibodies to selectively extract cells expressing PDX1 and ALK3, cultured them in vitro and showed that those progenitors could proliferate in the presence of BMP-7 and differentiate into beta cells.

Together, those findings may help move researchers closer to developing regenerative cell therapies not only for type 1, but also potentially for type 2 diabetes.

Donor pancreatic islet cell transplantation has allowed some type 1 diabetics to live without insulin injections, but there are insufficient cells to treat millions of patients who can benefit.

Rather, research has focused primarily on creating more pancreatic cells for transplant from sources like embryonic stem cells, pluripotent adult stem cells and porcine islet cells.

"While these approaches have been relatively successful over the past three to four years, a lot of work remains to be done," Dominguez-Bendala said. "For example, pluripotent stem cells do not readily become fully functional beta cells in vitro."

A more efficient and potentially safer solution could lie in regenerating a patient's own insulin-producing cells, sidestepping the need to transplant donor tissue altogether and eliminating other immune-related pitfalls.

"The ability to offer regenerative strategies to restore pancreatic insulin production could one day replace the need for transplantation of the pancreas or insulin-producing cells in type 1 diabetes," said DRI director Camillo Ricordi.

"This would require abrogation of autoimmunity to avoid immune destruction of the newly formed insulin producing cells. [Therefore] our current efforts are converging on immune tolerance induction without the need for lifelong anti-rejection drugs," he said.

"We hope eventually to develop a regenerative treatment for diabetes," concluded Dominguez-Bendala. "There remains much preclinical work to do, but our intention is to test the hypothesis that these cells can be potentially activated in the pancreas of patients, without the need for transplantation."