Universal platelet cells—generated from human induced pluripotent stem cells—made their debut last week, courtesy of Advanced Cell Technology (Marlborough, MA). The possibility of producing platelets—the component of blood that stops bleeding on-demand and circumventing donor rejection—could be a game changer for both platelet transfusions and even other tissue transplants.
Universal platelets are free of the infectious agents found in donated versions, allowing companies to skip the mandatory steps of screening donors and testing blood. Platelets also lose their value over time—they cannot be frozen, unlike their plasma and red blood cell counterparts that make up blood. They only last at room temperature for up to five days and are more likely to be in short supply. The tantalizing idea of mass produced universal platelets pinged our radar here at WEEKLY. In this issue, we will examine the science behind the potential of universal platelet technology.
AXING THE MHC PROTEIN
Major histocompatibility (MHC) proteins reside on the surface of cells and tissues in our body, playing an important role in activating the immune reaction by alerting the immune system to the presence of a foreign invader. Certain specialized MHC proteins actually bind to antigens and present them to T-cells for inspection, deciding whether or not to destroy the unwelcome entity.
Organ donation rejection can occur when the MHC proteins on the surface of a donor organ are not the same as the proteins on the surface of the recipient’s. Platelet cells also have MHC proteins on their surface, which come into play in the same way during platelet transfusions.
Using genome-editing technology, scientists at ACT removed the gene required for the production of the MHC proteins in platelets. As a result, these universal platelets are not rejected by any recipient; however, it is a problem of special relevance to those who receive platelet transfusions on a regular basis, such as cancer patients undergoing chemotherapy or radiation therapy.
TERM OF THE WEEK: HISTOCOMPATIBILITY
The prefix “histo” is derived from the Greek word for tissue, so histocompatibility simply means tissue compatibility and is often used in the context of organ or tissue transplants.
Histocompatibility is determined by the MHC proteins on the surface of cells and tissues. It appears there are six different proteins that determine compatibility; the higher the number of identical proteins, the greater the chance an organ transplant will be successful. Only identical twins share all six proteins in common.
Do not ever expect to see aspirin setting up romantic dates between platelet cells because it is a known anti-coagulant—that is, it interferes with the body’s ability to form clots. Patients at risk for heart attacks and strokes are often prescribed low-dose aspirin therapy to reduce the risk of these lumpy platelet formations. The flip side is that stopping internal bleeding may prove to be difficult with patients on an aspirin regimen.
Aspirin reduces inflammation by inhibiting a chemical called COX1, giving aspirin its pain-relieving and fever-reducing properties. The inhibition of COX1 also makes platelets less sticky. In other words, they are less likely to clump together and initiate clot formation. The protective effect lasts for as long as the platelets exposed to the aspirin are in circulation, and up to five days after aspirin use has stopped. This prevents amorous platelet bonding in the near future.
FIGHTING EBOLA WITH BLOOD
When we donate blood, it is often separated into three component parts: red blood cells, platelets, and plasma. Red blood cells are the oxygen-carrying component that bears the A, B, and O antigens we associate with blood-typing. Platelets assist in blood clotting, and plasma is everything else—a pale, yellow liquid that makes up about 55% of the body’s total blood volume.
Plasma is about 95% water but also contains dissolved proteins, glucose, clotting factors, electrolytes, hormones, and antibodies: the proteins produced by our immune system to fight infectious diseases. In the current Ebola outbreak, plasma from individuals who survived the viral infection are used to treat freshly exposed patients via transfusion. The presumption is the plasma from a recovered patient contains antibodies to Ebola. Rapid recognition of the virus by the infused antibodies will alert an infected patient’s immune system, and hopefully put the virus out of commission.