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Stem cells as an arthritis vaccine
May 1, 2017

Stem cells as an arthritis vaccine

Brunger JM et al. Genome Engineering of Stem Cells for Autonomously Regulated, Closed-Loop Delivery of Biologic Drugs. Stem Cell Reports, April 2017.

Arthritis is an ancient disease that is associated with swelling and inflammation of the joints. It often results in stiffness, pain, and restriction of movement. In most cases of arthritis, the range of necessary treatments is very limited and common pharmaceutical treatments simply relieve the symptoms. However, a new study using stem cell technology may lead to the development of an arthritis vaccine that specifically targets inflammation in joints and stops pain before it even starts. Researchers used CRISPR technology, a revolutionary gene-editing tool, to reprogram mouse stem cells to combat inflammation caused by arthritis. These newly generated stem cells are called SMART (Stem cells Modified for Autonomous Regenerative Therapy). They are designed to develop into cartilage cells that produce anti-inflammatory agents. They also end up replacing damaged cartilage, reducing chronic arthritis-related inflammation. Researchers hope to package these reprogrammed stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint, but only when needed. Current arthritis medications are given systemically, meaning they have the potential to interfere with other parts of the body. Since SMART cells deliver the medication only to the targeted location, this will significantly reduce the systemic effects.  The question is: will they be effective? In trials, SMART cells were observed to grow into cartilage tissue and even protect against inflammation over the course of a few days in mice.  Further testing is still in its initial phase in mouse models.  These stem cells have been engineered to fight rheumatoid arthritis.

Plastic-eating caterpillars

Bombelli P. et al. Polyethylene bio-degradation by caterpillars of the wax moth Galleria mellonella, Current Biology, April 2017.

Plastics are made of synthetic materials consisting of polymers, long strings of molecules derived from fossil fuels. Since they have a half-life of approximately 450 years, every piece of plastic that has ever been made is with us today, except for the very small amount that we've burned. Polyethylene, from which plastic bags are manufactured, is one of the plastic types that is the most resistant to degradation. Since stores give out more than one trillion polyethylene plastic bags every year, these indestructible plastics are accumulating all over the globe and pose serious environmental problems.  Scientists have long been searching for effective and environment-friendly solutions to eliminating plastic trash. One approach is to exploit simpler organisms, as they can be adept at utilizing unusual energy sources. After a lot of trial and error, researchers found that larva of a common insect, Galleria mellonella, is able to biodegrade polyethylene. Galleria mellonella, whose larvae are also known as waxworms, was discovered to do a significant amount of damage to a plastic bag in less than an hour. The follow-up tests detected the presence of the basic building block of polyethylene, ethylene glycol, in the waxworms' guts, demonstrating that the waxworms were indeed digesting polyethylene; they were not merely chewing it up into smaller pieces that passed through their guts unaltered. These results were initially puzzling to scientists; they couldn’t understand how waxworms were able to digest a substance that had only begun to be manufactured in the last century. The answer came from the ecology of the waxworm itself. Waxworms are a well-known pest to beekeepers, as they grow and feed on wax and honey. Since wax is a polymer with a very similar chemical structure to polyethylene, waxworms seem to already know how to digest polymer structures like plastics. Scientists still don’t know whether the polyethylene digestion is done by the waxworm itself or if it is relying upon the bacterial flora within its gut. As they learn more about the digestion mechanisms, they hope to design practical and effective biotechnological solutions for managing plastic waste, which will ultimately protect our oceans, rivers, and overall environment.

Pill for exercise?

Weiwei F et al. PPARδ Promotes Running Endurance by Preserving Glucose. Cell Metabolism, May 2017.

The benefits of exercise are well-known. Unfortunately, there are people who are obese, elderly, or mobility-limited and cannot benefit from exercise. To offer them a solution, scientists discovered a drug called GW1516 which mimics the beneficial effects of exercise, including an increased stamina and a higher rate of fat burning. While the control mice could only run 160 minutes on a treadmill, mice with the experimental drug lasted 270 minutes—about 70 percent longer. The discovery of GW1516 came from scientists’ previous knowledge of genetics. Scientists already knew that genetically activating the gene called PPAR delta enabled mice to run a lot longer than normal without getting tired.  Moreover, these mice are much less likely to gain weight or become diabetic. Scientists basically designed a chemical compound that activates the PPAR delta. The research team also analyzed the wide range of physiological effects of GW1516.  While the genes that break down fat for energy did more work in the mice with GW1516, genes that break down carbs for energy did less work. This is somewhat expected, as the bodies of really fit people typically burn fat, not carbs, for fuel. Despite these differences, GW1516 didn’t improve muscle mass. The only benefit seems to come from changing how the body breaks down energy. Although the initial studies have been done in mice, scientists are eager to develop clinical trials for humans as soon as possible.