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Can Artificial Cells Take Over for Lost Insulin-Secreting Cells?

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artificial beta cells

Caption: Artificial beta cell, made of a lipid bubble (purple) carrying smaller, insulin-filled vesicles (green). Imaged with cryo-scanning electron microscope (cryo-SEM) and colorized.
Credit: Zhen Gu Lab

People with diabetes have benefited tremendously from advances in monitoring and controlling blood sugar, but they’re still waiting and hoping for a cure. Some of the most exciting possibilities aim to replace the function of the insulin-secreting pancreatic beta cells that is deficient in diabetes. The latest strategy of this kind is called AβCs, short for artificial beta cells.

As you see in the cryo-SEM image above, AβCs are specially designed lipid bubbles, each of which contains hundreds of smaller, ball-like vesicles filled with insulin. The AβCs are engineered to “sense” a rise in blood glucose, triggering biochemical changes in the vesicle and the automatic release of some of its insulin load until blood glucose levels return to normal.

In recent studies of mice with type 1 diabetes, researchers partially supported by NIH found that a single injection of AβCs under the skin could control blood glucose levels for up to five days. With additional optimization and testing, the hope is that people with diabetes may someday be able to receive AβCs through patches that painlessly stick on their skin.


Snapshots of Life: Biological Bubble Machine

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plasma membrane vesicles

Credit: Chi Zhao, David Busch, Connor Vershel, Jeanne Stachowiak, University of Texas at Austin

As kids, most of us got a bang out of blowing soap bubbles and watching them float around. Biologists have learned that some of our cells do that too. On the right, you can see two cells (greenish yellow) in the process of forming bubbles, or plasma membrane vesicles (PMVs). During this blebbing process, a cell’s membrane temporarily disassociates from its underlying cytoskeleton, forming a tiny pouch that, over the course of about 30 minutes, is “inflated” with a mix of proteins and lipids from inside the cell. After the PMVs are fully filled, these bubble-like structures are pinched off and released, like those that you see in the background. Certain cells constantly release PMVs, along with other types of vesicles, and may use those to communicate with other cells throughout the body.

This particular image, an entrant in the Biophysical Society’s 2017 Art of Science Image Contest, was produced by researchers working in the NIH-supported lab of Jeanne Stachowiak at the University of Texas at Austin. Stachowiak’s group is among the first to explore the potential of PMVs as specialized drug-delivery systems to target cancer and other disorders [1].

Until recently, most efforts to exploit vesicles for therapeutic uses have employed synthetic versions of a different type of vesicle, called an exosome. But Stachowiak and others have realized that PMVs come with certain built-in advantages. A major one is that a patient’s own cells could in theory serve as the production facility.


Merry Microscopy and a Happy New Technique!

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Color EM Wreath

Seasons Greetings! What looks like a humble wreath actually represents an awe-inspiring gift to biomedical research: a new imaging technique that adds a dash of color to the formerly black-and-white world of electron microscopy (EM). Here the technique is used to visualize the uptake of cell-penetrating peptides (red) by the fluid-filled vesicles (green) of the endosome (gray), a cellular compartment involved in molecular transport. Without the use of color to draw sharp contrasts between the various structures, such details would not be readily visible.

This innovative technique has its origins in a wonderful holiday story. In December 2003, Roger Tsien, a world-renowned researcher at the University of California, San Diego (UCSD), decided to give himself a special present. With the lab phones still and email traffic slow for the holidays, Tsien decided to take advantage of the peace and quiet to spend two weeks alone at the research bench, pursuing an intriguing, yet seemingly wacky, idea. He wanted to find a way to deposit ions of a rare earth metal, called lanthanum, directly into cells as the vital first step in creating a new imaging technique designed to infuse EM with some much-needed color. After the holidays, when the lab returned to its usual hustle and bustle, Tsien handed off his project to Stephen Adams, a research scientist in his lab, thereby setting in motion a nearly 13-year quest to perfect the colorful new mode of EM.