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Cells Under Pressure

Posted on December 27, 2018

Scientists have uncovered what determines the fate of immature cells in the pancreas. The discovery could mean new treatments for individuals with type 1 diabetes.

The discovery reveals that immature islet cells are heavily influenced by their local environment and that these cells are very mobile.

The islets, also known as islets of Langerhans, are endocrine cells in the pancreas that produce the hormones insulin and glucagon and secrete them into the bloodstream. These hormones help to regulate the level of glucose (sugar) in the blood.

For individuals living with type 1 diabetes, the pancreas produces little or no insulin. Without the proper insulin levels, glucose, which is necessary for energy, cannot get into cells and builds up in the bloodstream. Too much sugar in the blood can leave type 1 diabetes patients at risk of complications such as nerve damage, blindness and kidney disease.

“When blood sugar goes unregulated, things change in the body and can get out of control quickly,” said Dr. Joel Singer, a New York regenerative medicine physician.

Other complications of uncontrolled blood sugar include heart disease, eye damage, stroke and skin problems.

The primary treatment for type 1 diabetes is lifelong insulin therapy. Insulin therapy helps to lower the amount of glucose in the blood, which lowers blood glucose, allows the body to use glucose for energy and reduces the risk of diabetes-related health complications.

The study, conducted by the Helmholtz Zentrum München – German Research Center for Environmental Health, recently published in the journal Nature, will potentially help diabetes researchers create pancreatic islet cells from stem cells.

This is not the first study to investigate new treatments for type 1 diabetes; other projects have examined the potential of developing insulin-producing beta cells from human pluripotent stem cells.

During the Helmholtz Zentrum München study, researchers were able to map the signal that causes pancreatic progenitor cells to become endocrine cells, such as those that produce insulin.

The additional insight gained during the study revealed that the development of immature islet cells in the pancreas is influenced by other cells in the environment and what is happening around them.

Immature islet cells can divide themselves into new cells and can also differentiate into mature islet cells in a capacity similar to stem cells. But, that is where their similarities end; their ability to self-renew is limited compared to stem cells.

Immature cells are also harder to study than stem cells because of how they behave and change. The German researchers overcame this obstacle by seeding human stem cell-derived progenitor cells on glass slides covered in varying patterns of matrix proteins. This allowed them to study how each cell behaved and reacted to its environment without changing under the influence of other cells.

This approach revealed something surprising: Researchers saw that interaction with different components in the environment change the mechanical force state within the immature cell.

They noticed that when the cells were exposed to laminin, a type of protein in the extracellular matrix, the mechanical forces within were decreased and cells developed into endocrine cells. When the cells were exposed to fibronectin, the mechanical effects on the cells increased, and the immature cells became duct cells.

This discovery will allow the researchers the chance to produce large numbers of pancreatic cells, which could mean new hope for type 1 diabetes patients. The study authors hope to use their approach for other conditions such as neurodegenerative conditions as well.

Source:

Helmholtz Zentrum München – German Research Center for Environmental Health. “Next step towards replacement therapy in type 1 diabetes.” ScienceDaily. ScienceDaily, 28 November 2018.

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