How to make better beta-cells?

A new collaborative paper. See it here!

​One of the more exciting developments in the past decade has been the ability to make insulin-producing pancreatic "beta" cells from stem cells. This is cool for many reasons: they are interesting models to study insulin and diabetes; they are a potential source of cells for transplantation and treatment of diabetes; and they may even eventually allow us to forego the use of immunosuppressants in such transplants.

But you'll notice that I put "beta" cells in quotation marks. That's because no one can currently make 'real' beta cells from stem cells in a dish. The cells that we currently make do produce some insulin, they can secrete that insulin, and to some degree they respond to the normal signals (like sugar) to control the release of insulin. But the current consensus is that stem cell derived beta cells still fall short of being 'real' beta cells - and for this reason they are variously referred to as 'stem-cell-beta cells' or 'beta-like cells'. Basically, the beta cells made from stem cells are usually considered immature, with properties that are more like the beta cells found very early in life!

So how can we tell when a stem cell is becoming a 'mature' beta cell? That's where markers come into the picture. What kinds of molecular signs can tell us whether a "beta" cell is becoming mature? That's the question asked by our friend Dr. Francis Lynn, Carmen Bayly and their team. Prior indications suggested mature "beta" cells have higher levels of something called 'islet amyloid polypeptide' or IAPP (side note - IAPP may actually be involved the development of diabetes - see here). Dr. Lynn and his team wanted to know if the stem-cell derived "beta" cells with higher levels of IAPP are, in fact, more mature. To answer this, they put a red fluorescent indicator that turns on when IAPP goes up into stem cells along with a green fluorescent indicator that turns on when insulin is present. They did this using CRISPR, which you might have heard of since it recently won the Nobel Prize for its discoverers. So, when stem cells are prodded to turn into "beta" cells the green signal turns on to indicate insulin is being made. Then, in some of those green cells, a red signal also turns on to indicate that IAPP is present.

So...what's the difference between the green cells and the green/red cells? When they studied the green and the green/red cells separately, they found that the latter had characteristics that more closely resembled 'mature' beta-cells from human donors. They had better glucose control of insulin secretion and better-regulated electrical activities (that's the work that we contributed). So what this mean? Using IAPP as a 'marker' for more mature beta-cells will be an important tool in discovering approaches (like drugs or other manipulations) that can help make better, more mature, 'beta-like cells' from stem cells for use in transplantation, research studies, and other applications.

Although clinical trials are underway, there is still a long way to go before stem-cell beta-cells will be widely available for transplantation. Improved tools (like the IAPP-reporter cells here) will be essential in making this happen!
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