Scientists Reprogram Human Pancreatic Cells to Produce Insulin

Human pancreas tissue typically contains about 1 billion beta cells, the main producers of insulin. Because these cells are missing or malfunctioning in people with diabetes, scientists have sought ways to replenish them as a long-term treatment and potential cure. A team of researchers has moved closer to that goal by genetically modifying another type of pancreatic cell to produce and release insulin when blood sugar levels rise.

Turning pancreatic ductal cells into insulin-producing cells

The researchers manipulated ductal cells, which previous studies have shown can sometimes transform into beta cells on their own. This is unusual in adult cells, whose identities tend to remain tightly fixed. The phenomenon suggested that ductal cells could be a promising starting point for generating new insulin-producing cells.

Until now, scientists did not know which genes caused this transformation, said Jiang Li, a postdoctoral fellow at Harvard Medical School who led the study, published in Science Translational Medicine. The researchers used a technique called genetic screening, which breaks down small pieces of DNA throughout the genome to identify those involved in specific biological processes.

The approach is similar to removing individual parts of a car engine without a schematic and observing which functions fail. This can reveal which parts are involved in fuel delivery or are essential for steering.

The researchers discovered that suppressing a gene called ALDH3B2 caused ductal cells to transform into beta-like cells at a higher rate. Without genetic changes, fewer than 1 percent of ductal cells spontaneously became beta-cell-like. When ALDH3B2 was suppressed, that percentage rose to about 8.5 percent.

Reprogrammed cells lowered blood sugar in diabetic mice

The initial experiments were performed on human cells grown in laboratory dishes. The researchers then transplanted the cells into diabetic mice. Human insulin began circulating in the mice, and their blood sugar levels fell to near-normal levels. The effects lasted for six weeks.

A potential alternative to transplanting new insulin-producing cells

Scientists have previously investigated several gene therapies for diabetes in hopes of providing long-term symptom relief. For example, a clinical trial launched earlier this year is taking a creative approach by giving muscle cells genetic instructions to produce insulin. Other treatments aim to generate new insulin-producing cells in the laboratory and transplant them into patients.

Cell transplantation comes with risks, including activation of the immune system. The new study suggests another possibility: using cells already present in the pancreas and changing their function by turning off genetic switches that maintain their identity.

Safety and precision remain major challenges

The approach also faces significant hurdles, including the need to ensure that only the intended cells are edited. ALDH3B2 is used by many cells throughout the body, not just pancreatic cells, so precision will be important to avoid unexpected complications.

Important questions also remain about how the gene helps transform ductal cells into beta cells. “That’s the part we need to look at first,” Lee said. “The next step is to find a gene therapy or specific small molecule that inhibits this gene to see if we can achieve a similar or even better effect.”

Even a partial improvement could have a major impact on the lives of an estimated 830 million people with diabetes worldwide, some of whom die each year from related complications.

This story was originally published in the Spanish version of WIRED and translated from Spanish.