Embryonic stem cells hold key to beta-cell transplantation in diabetes, but hurdles remain

BOSTON — Human embryonic stems cells may soon serve as a source for insulin-producing beta cells for patients with type 1 and type 2 diabetes; however, several challenges remain before cell transplantation becomes reality, according to a speaker at the Endocrine Society’s 98^th annual meeting.

Speaking during a presidential plenary discussion on the creation of human pancreatic beta cells for study and treatment of diabetes, Douglas A. Melton, PhD, co-director of the Harvard Stem Cell Institute and an investigator with the Howard Hughes Medical Institute, said that despite advances in the field of diabetes, a fundamental problem remains — a patient still relies on a blood glucose monitor to determine how much insulin to inject.

Douglas A. Melton

“Today I am going to talk about an extremely straightforward approach to try to replace insulin injections and blood glucose monitors by providing patients with the cells that do both of those things,” Melton said.

Insulin-producing cells have been successfully generated from human pluripotent stem cells, Melton said, but in previous attempts, they lacked the functional characteristics of mature beta cells. Melton and colleagues at the Stem Cell Institute developed stem cell-derived beta cells that expressed the markers of mature beta cells, including glucose-stimulated insulin secretion, and in large enough quantities needed for human cell transplantation, opening the door for future clinical trials in humans.

“Their gene expression is not identical, but it is very similar to adult human beta cells,” Melton said.

The cells, Melton said, also responded well to glucose challenges in mouse models.

The differentiation process was at times “exceedingly difficult,” Melton said, in part because the cells were created ex-vivo in the absence of any of the normal stimuli cells have during development.

“To get from an embryonic stem cell to a functional beta cell isn’t trivial; it’s not a one-step process,” Melton said. “We tested more than 70 different factors in more than 150 different combinations. You can do the math on how complicated that is.”

In cluster identification, Melton and fellow researchers found 14 different cell types in donor islets, including alpha and delta cells, which Melton’s lab has also been able to create.

“Our challenge in my lab now is can we make an islet?” Melton said. “I’ve shown we can make a beta cell, and now I want to make an islet.”

The final “hurdle,” Melton said, is to protect beta cells that would be transplanted in humans from an attack by the body’s own immune system. The Harvard Stem Cell Institute recently collaborated with the David H. Koch Institute for Integrative Cancer Research at MIT and other institutions to develop an implantable device that will shield the beta cells from attacks for several months in mouse models.

ViaCyte is also conducting a clinical trial, STEP ONE, using pancreatic progenitor cells and an encapsulation delivery system designed to protect the cells from a patient’s immune system, Melton said.

“I can tell you [beta-cell transplantation] won’t happen next year, but I would be very disappointed if it didn’t happen within a decade,” Melton said. – by Regina Schaffer

Reference :

Melton, DA. PL1-1. Presented at: The Endocrine Society Annual Meeting; April 1-4, 2016; Boston.

Disclosure: Melton reports no relevant financial disclosures.