Type-1 Diabetes is an autoimmune disorder which results in
the destruction of beta cells within the pancreas. A promising treatment
strategy is the replacement of the lost beta cell mass through implantation of
immune-isolated microencapsulated islets referred to as the bioartificial
pancreas. The beads are coated with a substance that allows insulin to pass
through, but prevents the body from recognizing the cells as “foreign” and
rejecting them. With this approach, there would be no need for anti-rejection
drugs.
A major challenge with this strategy is how to supply the
oxygen needs of the cells until the bio artificial pancreas forms its own blood
vessels. Insulin-producing cells have high oxygen requirements – they use 10 to
12 percent of the blood flow to the pancreas while accounting for only 1 to 2
percent of its weight. During the process of isolation, microencapsulation, and
processing prior to transplantation, the islets’ oxygen supply is disrupted,
and a large amount of islet cells are therefore lost due to extended hypoxia,
thus creating a major barrier to clinical success with this treatment. A continuous supply of oxygen is needed from the time
that the cells are first isolated from a donor pancreas until the bioartificial
organ is implanted and develops its own blood vessels, typically five to 10 days
post-transplant,” said Opara.
Researchers from Wake Forest
Institute for Regenerative Medicine found that the oxygen
provided by sodium percarbonate (SPO) and calcium peroxide (CPO) improved the
function and viability of insulin-producing cells during important stages of
the pancreas-building process. Sodium percarbonate is found in laundry
detergents and household cleaners, and calcium peroxide, is used as an
antiseptic and in many other ways.
Using insulin-producing cells isolated from rats and pigs,
the researchers conducted three studies: adding SPO during cell isolation;
evaluating the use of SPO particles during the cell growth process; and assessing
whether adding CPO particles during encapsulation would improve cell quality
during a week in a low-oxygen environment similar to what the cells would
encounter in the human body.
In all studies, the researchers were able to increase the
number of living cells by approximately 50 percent and their ability to make
insulin by eight times with the addition of oxygen. They learned that some
variables, including temperature, could be used to control oxygen levels.
If encapsulated pancreatic cells prove to be work in humans,
then it can eliminate the need to take insulin by injections or pump. Daily
monitoring of glucose by pricking your finger will not be compulsory.
John P. McQuilling, Sivanandane Sittadjody, Samuel
Pendergraft, Alan C. Farney, Emmanuel C. Opara. Applications of
particulate oxygen-generating substances (POGS) in the bioartificial pancreas. Biomater.
Sci., 2017; DOI: 10.1039/C7BM00790F
Thanks for posting Prava! I was interested in why SPO and CPO were specifically chosen. One thing I was able to find was an article which talked about using CPO as an oxygen releasing compound in soils (specifically, water aquafying treatment walls- which I'm still not entirely clear on). They reported that CPO is able to release oxygen over a longer period compared to other substances (Reaction: CaO2 + 2H2O --> Ca(OH)2 + 1/2 O2 + H2O) and also has a high mass purity when produced commercially (~60-80%). I bet these factors play a role in why it was chosen for human cell growth. Of note, calcium peroxide appears to play in an important role in regulating parathyroid function, which is important to consider when planning human trial feasibility.
ReplyDeleteChevalier, LR., & McCann, CD (2008). Feasibility of calcium peroxide as an oxygen releasing compound in treatment walls. Southern Illinois University Cabondale OpenSIUC Department of Civil and Environmental Engineering. http://opensiuc.lib.siu.edu/cgi/viewcontent.cgi?article=1002&context=cee_pubs
Brown, EM (2015). Control of parathyroid hormon secretion by its key physiological regulators. The Parathyroids (3). http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/calcium-peroxide