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False-colour image of cells comprising an islet of Langerhans, the endocrine component of the human pancreas. Beta cells secreting insulin are shown in green and orange (Image: CNRI/SPL)
Could a cure for diabetes come from within our brains?
Japanese scientists have taken neural stem cells from rats’ brains and transformed them into pancreatic cells that produce insulin to treat diabetes, New Scientist reports.
The work with the cells didn’t involve any genetic manipulation outside the body, a significant improvement to such experimentation.
When other labs attempted to alter stem cells from other parts of the body, alterations or genetic manipulations were necessary, but that raises safety concerns when transferring the treatment to humans.
Researchers reporting in the journal EMBO Molecular Medicine said they believe it would be possible to safely extract neural stem cells from humans using an endoscope.
The latest work involved exposing the cells to Wnt3a, a human protein responsible for turning on insulin production, and to an antibody that stops a natural inhibitor of the production of insulin.
Rats with both Type-1 and Type-2 diabetes who received treatment showed normal blood glucose levels within a week.
A cure for diabetes could be sitting in our brains. Neural stem cells, extracted from rats via the nose, have been turned into pancreatic cells that can manufacture insulin to treat diabetes.
Beta cells in the pancreas produce insulin, which regulates glucose levels. People with diabetes either have type 1, in which native beta cells are destroyed by the immune system, or type 2, in which beta cells cannot produce enough insulin.
To replace lost or malfunctioning beta cells, Tomoko Kuwabara of the National Institute of Advanced Industrial Science and Technology in Tsukuba Science City, Japan, and colleagues turned to neural stem cells in the brain.
Nasal extraction
First, they extracted a tiny amount of tissue from the rats' olfactory bulb, the part of the brain which deals with smell, or from the hippocampus, involved in memory. Each area is accessible through the nose, both in rats and humans.
Next, the team extracted neural stem cells from the tissue and exposed them to Wnt3a – a human protein that switches on insulin production – and to an antibody that blocks a natural inhibitor of insulin production.
After multiplying the stem cells for two weeks, they placed them on thin sheets of collagen which act as a removable scaffold. This allowed the team to lay the sheets incorporating the cells on top of the rats' pancreas without harming the organ itself.
Within a week, concentrations of insulin in the blood of both type 1 and type 2 rats that had received treatment matched those in non-diabetic rats. Elevated blood glucose concentrations also returned to normal.
The cells successfully tackled diabetes for 19 weeks until researchers halted the treatment by removing the sheets of cells, after which the rats' diabetes returned.
Natural change
Crucially, the cells did not have to be genetically manipulated outside of the body.
Many other labs around the world have tried altering stem cells from other parts of the body, including the gut, the liver and blood, to change them into beta cells. But these all require alterations or genetic manipulations which could pose safety concerns when transferring the treatment to humans.
Because the cells in the current study come from the same animal in which they are transplanted, they also overcome hurdles of rejection or the need for immunosuppressive drugs, such is the case when people receive donor pancreatic cells.
No manipulation
The researchers believe that it would be safe to access neural stem cells in humans. "It would be possible to extract adult neural stem cells from the olfactory bulb surgically using an endoscope," they say, adding that other groups have already done such extractions, proving that they are practical.
"The most important improvement offered by this study is the derivation of insulin-expressing cells from diabetes patients without the need for genetic manipulation," say Onur Basak and Hans Clevers of the Hubrecht Institute for Development Biology and Stem Cell Research in Utrecht, the Netherlands, in a commentary published alongside the work (EMBO Molecular Medicine, DOI: 10.1002/emmm.201100178).
"It will be essential to validate these results in available human neuronal stem cell lines as well as patient-derived olfactory bulb neural stem cells," they add.
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