The entire stem cell pharma drug industry is based on a key point sold to investors by companies pursuing the holy grail of stem cells in a vial. While transplanting a kidney or a heart would require tissue matching and very dangerous long-term use of anti-rejection drugs, getting someone else’s stem cells shouldn’t require any of this as foreign stem cells can’t be detected as foreign. We are only now beginning to see that this is only half true. Billions have been gambled on a factoid that if wrong, may create a world where the only truly effective stem cell therapy is using your own cells. Let me explain.
I’ve blogged before about problems with the nascent stem cell drug industry gearing up to supply millions of vials of someone else’s stem cells to a hospital near you. One of the issues I’ve uncovered is that a push toward better financial profitability a midst overbearing regulatory costs has forced many companies to grow their cells far too long-dramatically decreasing the potency of the stem cells. I’ve also blogged on other studies showing that someone else’s stem cells provoke an immune response in the host patient as they differentiate. Let me explain that last one a bit more.
Your body is very efficient at recognizing foreign tissue. This is for good reason, as throughout history the introduction of something foreign into the body was always bad news. For example, getting hit with a spear in your side isn’t good. If the pointy end is left there after breaking off the long end, your body needs to wall off this item to prevent your untimely death. The first way it does this is to ask the spearhead and the bacteria it carries a password question of sorts. The white blood cells check to see if the right password is on the item (let’s say a bacteria). This is called an MHC Complex. If the cell (or the spearhead) doesn’t have the right answer to the password challenge to identify itself as a cell that should be in your body, the white blood cells sound the alarm and set in motion an attack mode. This can consist of a certain type of white blood cell known as a “Natural Killer Cell” being programmed to become a “terminator” to wipe out the foreign cells. In the end, this is why transplanting a kidney is a big deal, as the kidney cells will always provoke a serious immune attack. This problem is usually suppressed with dangerous drugs so the foreign kidney can survive in the host patient.
So what does all of this have to do with someone else’s stem cells? These stem cell drugs weren’t supposed to have this password problem because they didn’t have MHC complexes. When challenged, they would have no answer rather than the wrong answer, causing the white blood cells to be fooled into thinking nothing was wrong. Now it turns out that every month we’re discovering more scientific evidence that stem cells acquire these wrong MHC passwords as they differentiate into the type of cells that they are meant to repair. This is really bad news for companies developing stem cell drugs as it means their cells will be killed off by the patient’s immune system because drugs made with someone else’s stem cells cause rejection.
To add insult to injury, this week another research paper was published that looked at whether someone else’s stem cells used to repair cartilage would provoke an immune attack. The cells should have started out without MHC password problems. However, even in the undifferentiated state, the stem cells were able to be detected as foreign (this wasn’t supposed to happen according to the experts). In addition, as they differentiated to become cartilage cells, they acquired the wrong immune system passwords and the host began to mount an even bigger immune attack on the stem cells. The researchers even tried placing the cells into their own micro capsules to shield their foreignness from the body, but as the stem cells differentiated the body wasn’t fooled. They finally concluded that effectively using someone else’s stem cells may require the same type of dangerous immune suppressant drugs that organ transplant patients use.
The upshot? There is a mounting body of evidence that using someone else’s stem cells provokes the patient’s body to attack those stem cells as foreign. This is really bad news for stock market investors in stem cell companies that have promised that this wouldn’t happen. It also means that in the end, until we know more sophisticated ways to deliver stem cells or engineer them, the only effective stem cell therapy may be using your own stem cells.