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

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 progenitor cells 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 diabetes," 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.

In type 1 diabetes, the insulin-producing cells 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 donor cells, 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 pancreatic cells for transplant from sources like embryonic (hESc), pluripotent (hPSc) and adult stem cells, 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 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 and Stacy Joy Goodman Professor of Surgery.

Mirza Muhammad Fahd Qadir, Silvia Álvarez-Cubela, Dagmar Klein, Giacomo Lanzoni, Carlos García-Santana, Abelardo Montalvo, Fabiola Pláceres-Uray, Emilia Maria Cristina Mazza, Camillo Ricordi, Luca Alessandro Inverardi, Ricardo Luis Pastori, Juan Domínguez-Bendala.
P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics.
Cell Reports, Volume 22, Issue 9, 2408-2420. doi: 10.1016/j.celrep.2018.02.006.

Most Popular Now

Cannabis extract helps reset brain function in psy…

Research from King's College London has found that a single dose of the cannabis extract cannabidiol can help reduce brain function abnormalities seen in people with psyc...

For first time in 40 years, cure for acute leukemi…

Acute myeloid leukemia is one of the most aggressive cancers. While other cancers have benefitted from new treatments, there has been no encouraging news for most leukemi...

New cancer treatment uses enzymes to boost immune …

Researchers at The University of Texas at Austin have developed a new approach to treating cancer using enzyme therapy. The enzyme, PEG-KYNase, does not directly kill can...

Bayer accelerates six new startups

Changing the experience of health: that's the focus of the six startups which the Bayer G4A team has included in the Accelerator program this year. The young companies fr...

Novartis receives European Commission approval of …

Novartis today announced that the European Commission (EC) has approved Kymriah® (tisagenlecleucel, formerly CTL019). The approved indications are for the treatment of pe...

Shire completes sale of oncology franchise

Shire plc (LSE: SHP, NASDAQ: SHPG) announces today that it has completed the sale of its Oncology franchise to Servier S.A.S. for $2.4 billion. The franchise includes the...

Antioxidant reduces risk for second heart attack, …

Doctors have long known that in the months after a heart attack or stroke, patients are more likely to have another attack or stroke. Now, a paper in the Journal of the A...

Novartis to divest the Sandoz US dermatology busin…

Novartis today announced it has agreed to sell selected portions of its Sandoz US portfolio, specifically the Sandoz US dermatology business and generic US oral solids po...

New tablet production facility in Ingelheim: Cente…

Boehringer Ingelheim held a groundbreaking ceremony for the construction of a new production facility for innovative drugs. This new Solids Launch facility will focus on ...

SOLAR-1 trial of Novartis investigational alpha-sp…

Novartis today announced the global Phase III SOLAR-1 trial evaluating the investigational alpha-specific PI3K inhibitor BYL719 (alpelisib) has met the primary endpoint s...

Tezepelumab granted Breakthrough Therapy Designati…

AstraZeneca and its partner Amgen Inc. (Amgen) today announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for tezepelumab...

Pfizer terminates domagrozumab (PF-06252616) clini…

Pfizer Inc. (NYSE: PFE) announced that it is terminating two ongoing clinical studies evaluating domagrozumab (PF-06252616) for the treatment of Duchenne muscular dystrop...