Better beta: cells grown in lab may treat diabetes.

Scientists have found a way to produce large amounts of a type of pancreas cell that doctors have already successfully transplanted into people with type 1 diabetes. The cells, collected from donors, have been in such short supply (SN: 6/19//04, p. 398) that only 1 percent of people in need have received transplants.

Establishing a lab-grown line of beta cells could overcome this shortage, says Ji-Won Yoon of Chicago Medical School in North Chicago, Ill. In type 1 diabetes, the immune system kills beta cells, eliminating the body's source of insulin. Without that hormone, tissues can't process sugar, so people with diabetes rely on insulin injections.

In the October Nature Biotechnology, Yoon and an international team of researchers report a beta cell-production technique that could, in principle, solve the supply problem. Central to their technique is what the researchers call a "reversibly immortalized" line of human beta cells.

First, the researchers extracted beta cells from pancreases collected from human cadavers. Then, because these cells tend to die quickly outside the body, the team supplied them with genes that perpetuate cell replication.

Such immortalizing of cells comes with a risk: The cells may grow into tumors. To counter that, the researchers included a mechanism to shut off the replication. They incorporated a molecular marker that guides a DNA-excising enzyme to the site of the added genes. The excision is timed to take place after large amounts of beta cells have been produced but before the cells are transplanted.

Next, the researchers screened 271 of their altered beta cell lines to find the ones most suitable for transplants. They eliminated lines that produced tumors despite the removal of the immortalization genes, and they disregarded the lines that didn't produce insulin and other beta cell proteins. In the end, only one line passed both tests.

Using the winning beta cell line, the researchers cultured enough cells to transplant 3 million into each of 10 diabetic mice lacking immune activity. The team reports that these mice maintained normal blood-glucose concentrations for more than 30 weeks.

"What they're selling is an impressive proof of principle," according to Christopher Newgard of Duke University Medical Center in Durham, N.C. The lab-grown beta cells produce only 40 percent as much insulin as normal beta cells do, he notes. Therefore, more than 1 billion cells would be needed for a human transplant. This number "clearly requires large-scale cell growth," says Newgard. It might be difficult to keep tumor-causing mutations out of such a large number of cultured cells, he cautions.

Yoon's current goal is to mass-produce reversibly immortalized cells that are safe and effective enough to gain Food and Drug Administration approval for use in people.

He notes that his team's beta cells would still be at risk from immunological attack when transplanted. The researchers aim to eventually develop beta cell lines that can withstand such an attack.