Scientists Successful In Growing “Mini-Stomachs” That Produce Insulin When Transplanted

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A team of researchers has succeeded in creating mini insulin-producing organs that can be implanted into a diabetic animal to maintain glucose levels, progress towards what they consider the future of regenerative medicine.

The cells the researchers found are best at producing insulin when reprogrammed are pylotic cells — cells from the lower region of the stomach, called the “pylorus region.”

They think that these cells work best because they are naturally very similar to the pancreatic beta cells that normally carry out this function. What they do better than other cells is respond to high glucose levels by producing insulin to normalize blood sugar levels.

Engineered gastic mini organ – the green represents insulin cells and the blue gastric stem/progenitor cells

What the researchers first did with their mouse test subjects and what they think could be done for people are two different things.

With mice, the researchers initially reprogrammed cells in their stomachs with conversion genes to become beta cells, and then they destroyed the mice’s pancreatic beta cells, forcing their bodies to rely solely on the artificially created ones. While control mice died within eight weeks, mice possessing the reprogrammed cells lived as long as they were tracked (up to six months).

The researchers also found that pyloric cells had the advantage of naturally renewing themselves — when the researchers destroyed the cells they had created, new ones grew and produced insulin.

Engineered stomach

This transgenic experiment would not be used as treatment for diabetes in people, however. Instead, the researchers set about to try something new: they grew tiny stomachs to produce insulin.

They took pyloric tissue out of mice, reprogrammed it to express beta-cell functions, grew the cells in the form of a tiny ball of insulin-producing “stomach,” and put the ball back into the mice. When they destroyed these mice’s pancreatic cells, the engineered organ implants compensated, maintaining normal levels of glucose in five of 22 test animals.

Senior author Dr. Qiao Zhou of the Harvard University Department of Stem Cell and Regenerative Biology explained how they will bridge the gap from the current study to an application for people.

“We are working on two approaches to move this forward toward therapeutics,” Zhou told The Speaker. “One approach is to create engineered human stomach mini-organs from human iPS cells (induced pluripotent stem cells made from the fibroblasts of individual patients) that can produce insulin in culture, followed by transplantation. The other approach is to culture human stomach stem cells from patient biopsy samples, reprogram them into beta-cells in culture, and then transplant them back to the same person. We are making progress on both fronts.”

He also noted the promise offered by engineered therapeutic organs in general.

“The regenerative medicine field has been moving towards a very exciting future of making and engineering entire organs with a complex assembly of different cell types. It is still early but with enormous potential. These organs could replace or supplement the normal function of organs in our body that are failing due to disease or aging. Genetic and bioengineering could be further applied to endow the organs with new function. I believe this is very much the future of regenerative medicine.”

The researchers said they were excited about their success. Replacing insulin-producing pancreatic cells is something science has been trying to do for decades.

“The most surprising part of the study for me is that there are cells residing in your stomach that share surprising features with pancreatic beta-cells,” said Dr. Zhou. “They do not naturally make insulin, but I believe therapeutic methods can be found to “tickle” them to do so. If successfully, it will provide an new approach to treat diabetes.”

Images: The report
Report: Ariyachet et al.: “Reprogrammed stomach tissue as a renewable source of functional beta-cells for blood glucose regulation,” published in Cell.
Link to report

Dr. Frederick Banting Made Insulin Free

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When Canadian Doctor Frederick Banting discovered insulin, he turned down offers from big corporations that would have made him – and them — rich, by making insulin available only to those who could afford it. Instead, Banting said that insulin was his gift to mankind.

Diabetes began to be recognized as a top killer of humans in the early 20th century. A few months was the usual expectation for those diagnosed with the disease.

Many scientists devoted themselves to the search for the cure, but none were able to find anything other than improved diets to prolong life expectancy.

A military surgeon serving in WWI, a war that had diverted funds away from most medical research for years, Frederick Banting followed up on a research paper he read that hypothesized that diabetes was caused by a single substance in the pancreas. The author of the paper, Englishman Sir Edward Albert Sharpey-Schafer, dubbed the hormone “insulin.”

Because digestion destroyed insulin, Banting set out to find a way to extract the substance from the healthy pancreases.

Banting worked on his task at his alma mater Toronto University with Dr. J.J.R. Macleod, who believed the experiment Banting wanted to use had an almost 100% chance of failure, so Banting performed the operation while Scotsman Macloed was overseas playing golf.

Banting and his team dispensed with many of previous ideas about how to search for the cure, and went to the slaughter-house and obtained beef and pig pancreases to test. It worked well, but was extremely inconsistent. The team struggled to achieve a solution that would be both pure and nontoxic to humans.

A teenager on his deathbed was given the first human trial of the insulin treatment, which failed and caused an allergic reaction. Biochemist James B. Collip went back to work on the solution. A second dose was administered to the same youth with success, and his health thrived.

However, the medicine could not save the large number of dying diabetics because the challenge of mass production of pure insulin had not yet been met.

At this point, large pharmaceutical companies offered the Banting huge sums of money for the patent to insulin. They proposed an insulin clinic with Banting in charge, and would make the medicine available to all who could pay for it. Banting, however, said that insulin was his gift to mankind, and it would be available to everyone who needed it rather than a commodity for anyone’s profit.

However, mass production was necessary and the process of introducing human insulin production genes into bacteria, then collecting and purifying the product of the bacteria is not a simple task. There would be an inherent production cost to the treatment for diabetes.

The Canadian group teamed with a large American drug company which could provide funding, facilities and supplies, and Lily was soon distributing the drug around North America and saving thousands of lives. Life expectancy for diabetics rose from weeks to tens of years.

The work earned the team the Nobel Prize in 1923. Banting was also knighted, and Canada later honored the scientist by printing his portrait on the $100 bill.

By Andy Scott