For The First Time, Scientists Turn Human Stem Cells Into Insulin-Producing Cells

Although treatment of type 1 diabetes has come a long way since it was first described in Ancient Egypt, insulin injections and finger pricks are a daily part of life for many diabetics.

But researchers have just made a breakthrough that might one day make these technologies obsolete, by transforming human stem cells into functional insulin-producing cells (also known as beta cells) – at least in mice.

"We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies," explains one of the team member.

"This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes."

Type 1 diabetes is characterised by a loss of insulin due to the immune system destroying cells in the pancreas - hence, type 1 diabetics need to introduce their own insulin manually. Although this is a pretty good system, it's not perfect.

People with the condition can live mostly normal lives, but they do have an increased risk of problems such as kidney failure, heart disease, and stroke.

There are other methods of managing type 1 diabetes, such as introducing new beta cells or swapping out the damaged pancreas for a new one, but both of these options have limited availability, as the new cells or organs need to be taken from organ donors.

To get around the donor problem, researchers including the team  has been working on nudging stem cells into becoming fully functional pancreatic beta cells for the last few years, but there have been some issues in getting them all the way there.

"The cells we and others were producing were getting stuck at an immature stage where they weren't able to respond adequately to blood glucose and secrete insulin properly," he said.
"It has been a major bottleneck for the field." 

But when the team looked at the way these cells develop in the pancreas, they struck gold. Here, the cells separate from the rest of the pancreas and arrange themselves into protrusions called pancreatic islets.

The team investigated this process in a petri dish, artificially separating the pancreatic stem cells to reorganise them into the islet-like clusters they naturally form in the body. This arrangement allowed the pancreatic stem cells to mature and function much like regular insulin-producing cells do.

And even better, when these islets were transplanted into healthy mice, they found that the cells produced insulin in response to blood sugar levels in a matter of days.

Of course, as with any mouse study, we can't get too excited just yet - there's still quite a bit of work to be done before this becomes a helpful treatment for humans. For one, if you were to introduce new pancreatic stem cells into a type 1 diabetic, it's likely that the immune system would still destroy them.

This means that anyone undergoing this treatment would have to be on immune suppressors for the rest of their life, an issue that also comes with organ and cell donations.

But this latest step is still a huge step forward, and the team is now working on solving these other problems. For example, they are investigating whether CRISPR can be used to change the stem cells enough that they could fly under the radar of the overactive immune system.

"We're finally able to move forward on a number of different fronts that were previously closed to us," he added. "The possibilities seem endless."

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A fasting diet may help to reverse diabetes

A type of fasting diet may reprogramme pancreas cells, promote the growth of new insulin-producing pancreatic cells and reduce symptoms of Type 1 and Type 2 diabetes, a study has showed.

In the study, led by researchers from the University of Southern California, mice were placed on fasting mimicking diet (FMD) for four days each week which showed remarkable reversal of diabetes.

The mice regained healthy insulin production, reduced insulin resistance and demonstrated more stable levels of blood glucose -- even in the later stages of the disease, the researchers said in the paper published in the journal Cell.

The genes normally active in the developing pancreas of embryonic/foetal mice are reactivated in diabetic adult mice when cycling FMD with normal diets.

This increases production of the protein neurogenin-3 (Ngn3) and, as a result, promotes the creation of new, healthy insulin-producing beta cells.

Researchers also examined pancreatic cell cultures from human donors and found that, in cells from Type 1 diabetes patients, nutrients mimicking fasting also increased expression of the Ngn3 protein and insulin production.

"These findings warrant a larger FDA trial on the use of the Fasting Mimicking Diet to treat diabetes patients," said Valter Longo from the University of Southern California. 

"People with diabetes could one day be treated with an FDA-approved Fasting Mimicking Diet for a few days each month, eat a normal diet for the rest of the month, and see positive results in their ability to control their blood sugar by producing normal levels of insulin and improving insulin function," Longo added.


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Insulin-producing cells grown in lab

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 Scientists have successfully converted human skin cells into functional pancreatic cells, a breakthrough that may lead to a personalised cell therapy for diabetics, ending the need for insulin jabs. The new cells produced insulin in response to changes in glucose levels, and when transplaned into mice, protected the animals from developing diabetes researchers said. The study will allow scientists to scale up pancreatic cell production and manufacture trillions of the target cells in a controlled manner.

"Our results demonstrate for the first time that human adult skin cells can be used to efficiently and rapidly generate functional pancreatic cells that behave similar to human beta cells," said Matthias Hebrok director of the Diabetes Centre at University of California "This finding opens up the opportunity for the analysis of patient-specific pancreatic beta cell properties and the optimisation of cell therapy approaches," said Hebrok.

In the study , the scientists first used pharmaceutical and genetic molecules to reprogrammed skin cells into endoderm progenitor cells -early developmental cells that have already been designated to mature into one of a number of different types of organs.

With this method, the cells do not have to be taken all the way back to a pluripotent stem cell state, meaning the scientists can turn them into pancreatic cells faster. After another four molecules were added, the endoderm cells divided rapidly , allowing more than a trillion-fold expansion. The scientists then progressed these endoderm cells two more steps, first into pancreatic precursor cells, and then into fully-functional pancreatic beta cells.

"The final step was the most unique and the most difficult, as molecules had not previously been identified that could take reprogrammed cells the final step to functional pancreatic cells in a dish," said first author Saiyong Zhu, a postdoctoral researcher at the Gladstone Institute of Cardiovascular Disease.

"This cellular reprogramming and expansion paradigm is more sustainable and scalable than previous methods," said Sheng Ding, a scientist.

Newly found ‘insulin-producing’ pancreatic cells offer hope to diabetics

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A team of researchers has found potential source of insulin-producing cells in the adult human pancreas, offering new hope to diabetics.
Cells that express neurogenin 3 (NGN3) may one day be harnessed to create a plentiful supply of insulin-producing beta cells for the treatment of diabetes, the University of South Florida study suggests.
NGN3 is the master gene driving development of the human endocrine pancreas, including the beta cells that make and secrete the hormone insulin, which helps control blood sugar levels. In type 1, or juvenile, diabetes, insulin-producing beta cells are destroyed by the person’s immune system, and patients need insulin injections to survive. Patients with the more common type 2 diabetes, referred to as adult-onset diabetes, produce insulin but their bodies cannot use it properly, and they often require extra insulin.
In the study, researchers from the Children’s Research Institute, USF Health Morsani College of Medicine; Johns Hopkins University School of Medicine; and the University of Illinois at Chicago, detected the NGN3 protein in histologically normal pancreatic biopsies from two sources-cadavers and patients requiring biopsy for diagnostic purposes.
NGN3 expression in the adult pancreas was unexpected, because it cannot be detected in the adult rodent pancreas – only during fetal development, said principal investigator Michael Shamblott.
Now that researchers know these NGN3 cells are a normal part of adult human pancreas biology, they can learn to increase them and to coax them towards becoming differentiated pancreatic endocrine cells by using specific drugs, Shamblott noted, adding that the goal is to regenerate functional beta cells that can cure diabetes.
The study is published in the journal PLOS ONE.