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Unwinding a Stem Cell Breakthrough

April 12, 2012
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Researchers at the Children's Hospital of Philadelphia 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 cells, they 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.

The findings were published in last week's edition of Cell/Stem Cell.

"Our cell line offers a powerful new tool for modeling how many human diseases develop," said study leader Paul J. Gadue, a stem cell biologist in the Center for Cellular and Molecular Therapeutics at CHOP.

"Additionally, pancreatic beta cells generated from EP cells display better functional ability in the laboratory than beta cells derived from other stem cell populations."

In addition to producing beta cells, the researchers also directed EP cells to develop into liver cells and intestinal cells--both of which normally develop from the endoderm tissue layer early in human development.

The researchers manipulated two types of human stem cells --embryonic stem cells and induced pluripotent stem cells -- 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.

Like ESCs, iPSCs are able to develop into many other types of human cells. However, when undifferentiated ESCs or iPSCs are transplanted in animal studies, they form teratomas, tumors containing many different cell types.

Therefore, it has been critical that any cell type generated from ESCs or iPSCs and used for transplantation is stringently purified to exclude undifferentiated cells with tumor-forming potential.

In the current study, the researchers used signaling molecules called cytokines to steer ESCs and iPSCs into becoming EP cells.

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 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.

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