Unique pancreatic stem cells have potential to regenerate beta cells, respond to glucose

February 27, 2018, Diabetes Research Institute Foundation
Unique pancreatic stem cells have potential to regenerate beta cells, respond to glucose
Diabetes Research Institute scientists have confirmed that the unique stem cells reside within large ducts of the human pancreas. Two such ducts (green), surrounded by three islets (white) are shown. Credit: Diabetes Research Institute Foundation

Scientists from the Diabetes Research Institute at the University of Miami Miller School of Medicine have confirmed the existence of progenitor cells within the human pancreas that can be stimulated to develop into glucose-responsive beta cells. These significant findings, published in Cell Reports, open the door to developing regenerative cell therapies for those living with type 1 diabetes, addressing a major challenge that stands in the way of discovering a biological cure for the disease.

The notion that the pancreas harbors with the potential to regenerate islets has been hypothesized for decades, but not conclusively demonstrated. DRI scientists have now been able to identify the exact anatomic 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 ," said Juan Dominguez-Bendala, Ph.D., DRI director of pancreatic stem cell development for translational research and co-principal investigator of the study alongside Dr. Ricardo Pastori, Ph.D., director of molecular biology. "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."

The DRI team previously reported that bone morphogenetic protein 7 (BMP-7), a naturally occurring growth factor already approved by the Food and Drug Administration (FDA) for clinical use, stimulates progenitor-like cells within cultured human non-endocrine pancreatic tissue. In the most recent study, the researchers went on to demonstrate that those stem cells that respond to BMP-7 reside within the pancreatic ductal and glandular network of the organ. Additionally, the cells are characterized by the expression of PDX1, a protein necessary for beta cell development, and ALK3, a cell surface receptor that has been associated with the regeneration of multiple tissues. Using "molecular fishing" techniques, they were able to selectively extract the cells that expressed PDX1 and ALK3, grow them in a dish and demonstrate that they can proliferate in the presence of BMP-7 and later differentiate into beta cells. Together, the combined study results may help move researchers closer to developing regenerative cell therapies for type 1, and potentially type 2, diabetes.

Unique pancreatic stem cells have potential to regenerate beta cells, respond to glucose
Human pancreatic section showing the epithelium of a large pancreatic duct harboring progenitor-like cells. These cells are characterized by expression of PDX1 (white) and the BMP-7 receptor ALK3 (red), but not the ductal marker carbonic anhydrase II (CAII, green). When sorted and cultured in defined conditions, these cells are BMP-7-expandable and exhibit multipotent differentiation potential. Credit: Diabetes Research Institute Foundation

In type 1 diabetes, the of the pancreas have been mistakenly destroyed by the immune system, requiring patients to manage their blood sugar levels through a daily regimen of insulin therapy. In type 2 diabetes, patients are able to produce some insulin, but their beta cells may become dysfunctional over time. Islet transplantation has allowed some patients with type 1 diabetes to live without the need for insulin injections after receiving infusions of , however there are not enough cells to treat the millions of patients who can benefit. Thus far, research efforts have focused primarily on creating more for transplant from sources like embryonic (hESc), pluripotent (hPSc) and adult , and porcine (pig) islets, among others. 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 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 . In type 1 diabetes, this would require abrogation of autoimmunity to avoid immune destruction of the newly formed insulin producing . 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 and Stacy Joy Goodman Professor of Surgery.

Explore further: Growing pancreatic stem cells for research on diabetes

More information: Mirza Muhammad Fahd Qadir et al, P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics, Cell Reports (2018). DOI: 10.1016/j.celrep.2018.02.006

Related Stories

Growing pancreatic stem cells for research on diabetes

November 29, 2017
A new cell culture procedure developed by A*STAR will assist the study of diabetes and facilitate better treatments. "Our discovery will enable studies of how the pancreas forms and why certain cells malfunction in diabetes," ...

Researchers find potential source of insulin-producing cells in adult human pancreas

September 23, 2015
Cells that express neurogenin 3 (NGN3) may one day be harnessed to create a plentiful supply of insulin-producing beta cells for the treatment of diabetes, a study led by researchers at the University of South Florida suggests.

Scientists study how some insulin-producing cells survive in type 1 diabetes

February 9, 2017
A Yale-led research team identified how insulin-producing cells that are typically destroyed in type 1 diabetes can change in order to survive immune attack. The finding may lead to strategies for recovering these cells in ...

Pancreatic islets study may spur diabetes treatment advances

September 22, 2017
Investigators in the Vanderbilt Diabetes Research and Training Center (VDRTC) and collaborators at Stanford University have discovered new insights into the molecular mechanisms of cell proliferation in juvenile human pancreatic ...

Protein packaging may cause the immune attacks of type 1 diabetes

November 21, 2016
Type-1 diabetes occurs when immune cells attack the pancreas. EPFL scientists have now discovered what may trigger this attack, opening new directions for treatments.

Novel tissue-engineered islet transplant achieves insulin independence in type 1 diabetes

May 11, 2017
Scientists from the Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine have produced the first clinical results demonstrating that pancreatic islet cells transplanted within a tissue-engineered ...

Recommended for you

Belly fat promotes diabetes under orders from liver

March 21, 2018
The fat that builds up deep in the abdomen—more than any other type of body fat—raises the risk of insulin resistance and type 2 diabetes. Researchers have known that abdominal fat becomes dangerous when it becomes inflamed ...

Consuming low-calorie sweeteners may predispose overweight individuals to diabetes

March 18, 2018
Consumption of low-calorie sweeteners could promote metabolic syndrome and predispose people to prediabetes and diabetes, particularly in individuals with obesity, a new study on human fat-derived stem cells and fat samples ...

Are high blood glucose levels an effect rather than the cause of diabetes?

March 15, 2018
Insulin resistance and elevated blood glucose levels are considered to be the cause of type 2 diabetes. However, scientists from the German Cancer Research Center (DKFZ) and Heidelberg University Hospital have now provided ...

Smoking linked with higher risk of type 2 diabetes

March 15, 2018
The prevalence of diabetes has increased almost 10-fold in China since the early 1980s, with one in 10 adults in China now affected by diabetes. Although adiposity is the major modifiable risk factor for diabetes, other research ...

Social support and machine learning are at the core of a student-developed app for people with diabetes

March 14, 2018
Diabetes is the seventh leading cause of death in the U.S., and nearly 10 percent of the population suffers from this chronic disease, according to the Centers for Disease Control and Prevention.

Toxic proteins and type 2 diabetes

March 9, 2018
Nearly a half-billion people worldwide live with type 2 diabetes. Yet despite the disease's sizeable and increasing impact, its precise causes remain murky. Current scientific thinking points to two key processes: insulin ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.