Saturday, November 18, 2017

Bioartificial Pancreas

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 pancreasBiomater. Sci., 2017; DOI: 10.1039/C7BM00790F



1 comment:

  1. 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.


    Chevalier, 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

    ReplyDelete