Nav: Home

Diabetic mice improve with retrievable millimeter-thick cell-laden hydrogel fiber

June 15, 2020

Tokyo, Japan - Type 1 diabetes mellitus (T1DM) results from an irreversible autoimmune destruction of insulin-producing pancreatic β-cells requiring life-long substitution of insulin. In a new study, researchers at the Institute of Industrial Science, The University of Tokyo discovered that the diameter of cell-laden hydrogels determines its longevity after transplantation, paving the way for efficacious cell therapy for T1DM.

Current treatment strategies for T1DM focus on timed exogenous insulin administration, posing a significant burden on the patient as well as the health care system. Cell therapy aims at replacing lost pancreatic β-cells permanently, eliminating the need for insulin substitution. Although cell replacement therapy has been regarded as an attractive option for T1DM, its clinical success has been limited by immune-mediated foreign body reactions.

"Cell therapy suffers from a similar fate to that of organ transplantation, which is transplant rejection," says corresponding author of the study Shoji Takeuchi. "One way to mitigate this issue is to encapsulate pancreatic cells in hydrogels, although this does not prevent the transplant from foreign body reactions. We wanted to investigate how we can optimize hydrogels to provide long-term immunoprotection for transplanted cells."

The researchers hypothesized that the diameter of hydrogel fibers critically determines whether the cell transplant mitigates foreign body reactions. By implanting barium alginate (Ba-Alg) hydrogels with variable fiber diameters into normal mice, they showed that the threshold, above which immune reactions were significantly lower, appears to be at 1.0 mm. To investigate if the biological superiority comes at a biophysical expense, the researchers compared 1.0-mm- and 0.35-mm-thick Ba-Alg hydrogel fibers. Not only was the 1.0-mm-thick fiber easier to handle than the 0.35-mm-thick construct based on biomechanical measurements, it also allowed small molecules like glucose, insulin and oxygen to pass through the hydrogel membrane, all of which are required if cells encapsulated within the hydrogel are to function properly.

But did it keep its promise to facilitate cell therapy for T1DM? To address this, the researchers loaded rat pancreatic islet cells into 1.0-mm- and 0.35-mm-thick hydrogel fibers and tested how well the fibers performed in secreting insulin upon stimulation with glucose. Although cells in 0.35-mm-thick hydrogels performed better, cells in 1.0-mm-diameter-fibers functioned sufficiently well to test them in diabetic mice in the next step. Here, the researchers transplanted the two types of hydrogels in the intraperitoneal cavities of diabetic mice and measured daily non-fasting blood glucose levels. Strikingly, 1.0-mm-thick fibers normalized blood glucose levels of diabetic mice for a period over four times longer than 0.35-mm-thick fibers, suggesting a higher longevity of pancreatic cells encapsulated in thicker hydrogel fibers. Further, microscopic analysis showed no evidence of foreign body reactions of 1.0-mm-thick fibers, while 0.35-mm-thick fibers seemed to have deteriorated over time.

"These are striking results that show how hydrogel encapsulation in 1.0-mm-thick fibers provides long-term immunoprotection for pancreatic islets while maintaining their function to control blood glucose concentrations in diabetic mice," says Takeuchi. "Our findings provide new insights into cell therapy-based treatment of type 1 diabetes mellitus."
-end-
The article, "Millimeter-thick xenoislet-laden fibers as retrievable transplants mitigate foreign body reactions for long-term glycemic control in diabetic mice," is currently under review in Biomaterials

About Institute of Industrial Science (IIS), the University of Tokyo

Institute of Industrial Science (IIS), the University of Tokyo is one of the largest university-attached research institutes in Japan.

More than 120 research laboratories, each headed by a faculty member, comprise IIS, with more than 1,000 members including approximately 300 staff and 700 students actively engaged in education and research. Our activities cover almost all the areas of engineering disciplines. Since its foundation in 1949, IIS has worked to bridge the huge gaps that exist between academic disciplines and real-world applications.

Institute of Industrial Science, The University of Tokyo

Related Insulin Articles:

US Insulin prices 8 times higher than in other nations
Insulin list prices in the United States have increased dramatically over the past decade, with per person insulin spending doubling between 2012 and 2016.
A gatekeeper against insulin resistance in the brain
The brain plays a major role in controlling our blood glucose levels.
Sorting and secreting insulin by expiration date
Visualizing the age of insulin secreting granules in cells allowed researchers to investigate how cells' preference for secreting newer granules is disrupted in diabetes.
Researchers develop a new ultrafast insulin
Stanford researchers tested a new insulin drug in diabetic pigs and found that it was twice as fast-acting as traditional insulin.
Insulin signaling suppressed by decoys
The discovery of an insulin 'decoy' molecule from the lab of Matthew Gill, PhD, in Florida shakes up understanding of insulin signaling, with implications for diabetes, longevity and aging research.
New mechanism for dysfunctional insulin release identified
In a new study, researchers at Uppsala University have identified a previously unknown mechanism that regulates release of insulin, a hormone that lowers blood glucose levels, from the β-cells (beta cells) of the pancreas.
Type 2 diabetes is not just about insulin
Obesity, by promoting the resistance to the action of insulin, is a major risk factor of diabetes.
The insulin under the influence of light
By understanding how the brain links the effects of insulin to light, researchers (UNIGE) are deciphering how insulin sensitivity fluctuates according to circadian cycles.
Does insulin resistance cause fibromyalgia?
Researchers led by a team from The University of Texas Medical Branch at Galveston were able to dramatically reduce the pain of fibromyalgia patients with medication that targeted insulin resistance.
Insulin insights
Insulin triggers genome-wide changes in gene expression via an unexpected mechanism.
More Insulin News and Insulin Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.