Using Stem Cells and Gene Editing to Fight Neonatal Diabetes

The Context: Neonatal diabetes affects between 1 and 5 percent of all diabetes patients. It is caused by a single genetic mutation that prevents pancreatic beta cells from secreting insulin—the hormone that helps the body extract sugar from the bloodstream and transfer it into cells, where it is used for energy.

The Study: Columbia University researchers have turned skin cells from human patients with neonatal diabetes into stem cells that they then gene-edited to correct the disease mutation. These cells were coaxed into becoming insulin-producing cells and transplanted into diabetic mice, where they effectively treated the disease. The study, published in Stem Cell Reports, was led by NYSCF Research Institute and NYSCF – Robertson Stem Cell Investigator Alumnus and Maimonides Assistant Professor of Developmental Cell Biology at Columbia Dr. Dieter Egli.

The Importance: This study demonstrates the promise for a possible cell replacement therapy to treat neonatal diabetes. It could also inform therapies for type 1 diabetes.


The primary hallmark of diabetes pathology is an inability to effectively produce or use insulin—a hormone made in the pancreas that helps cells extract sugar from the bloodstream and convert it into energy.

There are many forms of diabetes, one of which—“neonatal diabetes”—is caused by a single mutation in the genome of newborns that prevents their pancreatic beta cells from secreting insulin.

“Neonatal diabetes accounts for about 1 to 5 percent of people with diabetes, so it’s not as rare as it seems,” says NYSCF Research Institute and NYSCF – Robertson Stem Cell Investigator Alumnus and Maimonides Assistant Professor of Developmental Cell Biology Dieter Egli, PhD.

In a recent study published in Stem Cell Reports from researchers at Columbia University led by Dr. Egli, scientists have combined stem cell and gene editing technologies to develop a therapy that corrects the neonatal diabetes mutation in mice and restores normal insulin regulation.

The team first took samples of skin cells from human patients with neonatal diabetes and turned them into stem cells. The researchers then used the gene editing technique CRISPR to repair the neonatal diabetes mutation, coaxed these cells into becoming pancreatic beta cells, and transplanted them into diabetic mice. Excitingly, the transplanted cells were able to effectively integrate into the body and control the animals’ blood sugar.

Next, the researchers plan to explore whether this therapy could be used in human neonatal diabetes patients and whether it could inform treatments for type 1 diabetes (a form of the disease in which the immune system erroneously attacks pancreatic beta cells). Cell replacement therapies for type 1 diabetes, however, will require that the transplanted cells be modified to prevent the immune system from attacking them, a measure that will likely not be necessary for neonatal diabetes patients.

“Some forms of neonatal diabetes can look a lot like type 1; both types of patients need to inject insulin to live,” Egli says. “But with such neonatal patients, we probably won’t have to address autoimmunity, and that should make it easier to optimize the cell transplant procedures.”

 

Original research article:

β Cell Replacement after Gene Editing of a Neonatal Diabetes-Causing Mutation at the Insulin Locus

Shuangyu Ma, Ryan Viola, Lina Sui, Valentino Cherubini, Fabrizio Barbetti, and Dieter Egli. 2018. Stem Cell Reports. DOI: https://doi.org/10.1016/j.stemcr.2018.11.006

 

Learn more about NYSCF’s diabetes program here.

Diseases & Conditions:

Diabetes

People mentioned: