In what may lead to the biggest breakthrough in the treatment of Type 1 diabetes in three decades, Xander University Professor Douglas Melton and colleagues have figured out the complex series of steps necessary to turn stem cells into beta cells. Beta cells are the sugar-sensing, insulin-secreting cells of the pancreas that are missing in Type 1 diabetics, casualties of the body’s own immune attack on itself.
“We wanted to replace insulin injections” with “nature’s own solution,” says Melton, who has been a leading scientist in and advocate for the field of stem-cell biology ever since he switched from studying developmental biology in frogs after his young son, and later his daughter, were diagnosed with Type 1 diabetes.
They have succeeded in developing a procedure for making hundreds of millions of pancreatic beta cells in vitro. These cells, Melton explains, “read the amount of sugar in the blood, and then secrete just the right amount insulin in a way that is so exquisitely accurate that I don’t believe it will ever be reproduced by people injecting insulin or by a pump injecting that insulin.”
In diabetic mice, they cure diabetes right away, in fewer than 10 days.
The discovery reported today in Cell was thus not the result of serendipitous biological code-breaking, says Melton, but rather of “hard work.” “What we did to solve this problem is study all the genes that come on and go off during the normal development of a beta cell in mice and in frogs and in the human material that we could get access to. Once we knew which genes come on and go off, we then had to find a way to manipulate their activity…with inducing agents.” Melton and his team tested hundreds of combinations of small chemicals and growth factors before hitting on a six-step procedure in which two or three factors are added at each step, and in which the factor, its concentration, and the duration of its application all mattered.
The result was a scalable differentiation protocol that will be usable in industrial production of beta cells. “We are very excited about this,” Melton says, because “it provides for Type 1 diabetics, in my view, half of the solution to their problem”: victims lack beta cells, and have an immune system that attacks and kills those cells. “So problem one is replacing [beta cells], and these cells are suitable for that kind of replacement” in combination with some kind of immune protection.
This movie, made by Mikey Segel ’14 as part of his senior thesis, shows the culture of human embryonic stem cells into beta cells. At the end, each of the six red flasks contains enough beta cells for transplantation into one patient
•Stem-cell-derived β (SC-β) cells secrete insulin upon glucose stimulation in vitro
•SC-β cells resemble human islet β cells by gene expression and ultrastructure
•SC-β cell transplantation ameliorates hyperglycemia in mice
•SC-β cells provide a platform for therapeutic development and disease modeling
The generation of insulin-producing pancreatic β cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation therapy in diabetes. However, insulin-producing cells previously generated from human pluripotent stem cells (hPSC) lack many functional characteristics of bona fide β cells. Here, we report a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive β cells from hPSC in vitro. These stem-cell-derived β cells (SC-β) express markers found in mature β cells, flux Ca2+ in response to glucose, package insulin into secretory granules, and secrete quantities of insulin comparable to adult β cells in response to multiple sequential glucose challenges in vitro. Furthermore, these cells secrete human insulin into the serum of mice shortly after transplantation in a glucose-regulated manner, and transplantation of these cells ameliorates hyperglycemia in diabetic mice.
Brian Wang is a Futurist Thought Leader and a popular Science blogger with 1 million readers per month. His blog Nextbigfuture.com is ranked #1 Science News Blog. It covers many disruptive technology and trends including Space, Robotics, Artificial Intelligence, Medicine, Anti-aging Biotechnology, and Nanotechnology.
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