Researchers have generated a new type of human stem cell that can develop into numerous types of specialized cells, including functioning pancreatic beta cells that produce insulin. Called endodermal progenitor (EP) cells, the new cells show two important advantages over embryonic stem cells and induced pluripotent stem cells: they do not form tumors when transplanted into animals, and they can form functional pancreatic beta cells in the laboratory.
“Our cell line offers a powerful new tool for modeling how many human diseases develop,” said study leader Paul J. Gadue, PhD, a stem cell biologist in the Center for Cellular and Molecular Therapeutics at The Children’s Hospital of Philadelphia. “Additionally, pancreatic beta cells generated from EP cells display better functional ability in the laboratory than beta cells derived from other stem cell populations.”
The researchers manipulated two types of human stem cells — embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) — to become EP cells. Because both stem cell populations proliferate in great numbers and potentially generate all types of tissue, they offer enormous promise for scientists to precisely control cell development, both for the study of basic biology and for future cell-based treatments.
ESCs are derived from human embryos, typically unused embryos from fertility treatments that are donated for research purposes, while iPSCs are engineered from human somatic cells, such as skin cells or blood cells. In the current study, the researchers used signaling molecules called cytokines to steer ESCs and iPSCs into becoming EP cells, committed to developing into endoderm, one of the three tissue layers found in early human development. The EP cells have nearly unlimited potential for growth in the laboratory.
Both in cell cultures and when transplanted into animals, the study team showed that EP cells can differentiate into multiple cell types, representing those found in the liver, pancreas and intestine. Importantly, undifferentiated EP cells did not form teratomas [tumors] in the team’s transplantation studies.
In cell culture, the researchers differentiated the EP cells into beta cells — insulin-expressing cells similar to those found in the pancreas. Those engineered beta cells passed an important test — when stimulated by glucose, they were able to release insulin, a function that is impaired or absent in patients with diabetes. While the cells achieved only 20 percent of normal function, this result is an improvement over that seen in similar cells derived directly from ESCs or iPSCs, which typically respond very poorly or not at all to glucose.
Finally, although applying this science to cell therapy is years away from practical clinical use, EP cells may offer a powerful starting point for developing tissue replacement treatments, such as supplying beta cells for diabetes patients or hepatocytes (liver cells) for patients with liver disease. “While more work is needed to characterize EP cells, they may offer a potential source of safe, abundant cells for future diabetes treatments,” said Gadue.
Health-e-Solutions comment: statements like, “…years away from practical use,” and, “…achieve only 20 percent of normal function,” and “…may offer a potential source of safe cells,” reveal the distance still to be travelled if this new cell source is to become helpful to those of us living with diabetes today. We believe that it is vital to keep our bodies as healthy as possible through optimal blood sugar control until the cure for diabetes comes along. We believe the diabetic-alkaline lifestyle has provided that healthy foundation for our boys.