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Harvard-born diabetes startup Semma reports advances in turning stem cells into insulin producers

Diabetes blood sugar testing
Semma Therapeutics hopes to cure Type 1 diabetes by perfecting a process for regenerating insulin-producing beta cells.

In November 2017, Harvard University scientist Douglas Melton made headlines when his startup, Semma Therapeutics, raised $114 million in a series B funding round to develop what he said would be a potential cure for Type 1 diabetes. His idea was to take undifferentiated pluripotent stem cells and turn them into insulin-producing pancreatic beta cells.

Problem was, only 30% of the cells that emerged from the transformation process Melton’s lab developed turned out to be functioning beta cells. Now, his team of researchers says they figured out how to improve their process so they can increase the proportion of beta cells to 80%. They published their findings in the journal Nature.

Improvements in single-cell gene sequencing made it possible for Melton’s lab to probe all of the cells they were making from stem cells as they tried to transform them into beta cells. They discovered wide variations in gene expression among the cells. Some expressed genes consistent with glucagon production, while others had gene-expression patterns consistent with the sought-after insulin-producing beta cells.

The researchers also found a protein that’s expressed only on beta cells. That discovery allowed them to develop a hook method that could “fish” beta cells out of the mixture of cells that emerged from their process, according to a statement from Semma.

Scientists at Semma developed a second method to further boost the population of beta cells. They hypothesized that hormone-producing cells would be more attracted to each other than they are to non-hormone producers. So they physically separated all the cells and let them cluster back together naturally. It worked: The clustering further enriched the number of beta cells in each sample of converted stem cells, they reported.

Semma was founded in 2014, raising $44 million in a series A funding. The company formed a partnership with Novartis, which contributed to Semma’s series B round along with medical devices giant Medtronic, MPM Capital, ARCH Venture Partners and several other venture capitalists. In May of last year, Novartis veteran Bastiano Sanna moved to Semma to take over as CEO.

As Semma moves through the proof-of-concept stage of its development, several other research groups are examining different methods for regenerating insulin-producing cells. In February, researchers at the University of Geneva reported promising results in mouse models of diabetes with human alpha and gamma endocrine cells that had been converted into insulin-producing cells.

A team at the University of Miami is working on converting specialized stem cells called progenitors into beta cells. And Stanford University scientists recently discovered that zinc can aid in regenerating insulin-producing beta cells.

The next step for Semma’s team is to determine whether a mixture consisting of 80% beta cells will be appropriate for treating people with diabetes. They are planning further studies to determine the optimal mix of cell types.

“Maybe you need more of the other cell types to help regulate the beta cells, so that they function correctly,” said lead author Adrian Veres, a graduate student in Melton’s lab, in an interview with the Harvard Gazette. “We’re going to find out how the cell types interact with each other.”