Sometimes luck favors the prepared mind

This week in the journal Cell: Stem Cell – Steven Goldman’s lab reported the successful transplant of stem cells into the brains of mice with a rare demyelinating disease. Within hours of the study’s release, the BBC and other news outlets were heralding it as a possible breakthrough in our ability to treat multiple sclerosis. While this study does represent some really significant technological advances, a little reality needs to be injected into the hype. Before we talk about what this study means to stem cell treatments, lets talk about a few of the technical problems with linking this series of experiments to human medicine.

1. The stem cells were partially differentiated glial cells (oligodendrocytes) harvested from the remains of five aborted human fetuses.
Regardless what you think about abortion, not many people would find it palatable for the remains of a fetus to be injected into their brains.
2. The stem cells were injected into diseased mice that had been genetically modified so that they do not have functioning immune systems. These mice (called rag -/-) cannot mount a specific immune response to anything, and must be kept in a sterile environment from birth. Simple bacterial and viral infections will kill them. This was necessary because mice will normally reject human tissues that are transplanted into their bodies. Needless to say – this is a HUGE hurdle that must be overcome before any kind of fetal tissue transplantation could be come feasible in humans.
3. The mice were injected in the cranial cavities (in the brain) within one day of birth. Long before any symptoms of this disease were evident, these mice were treated. Of course, that is because the researchers knew the mice would be diseased; they were engineered that way. Humans, on the other had, are not diagnosed with MS for many years after birth – at least for now.
4. MS is an autoimmune disease; “shiverer” mice are affected with a congenital disease. Some might think – aren’t all demyelinating diseases the same? No, they are actually quite different. From what we know now, MS is an autoimmune disease – the immune system begins attacking and killing the myelin in the central nervous system. Shiverer mice never really develop much myelin. In addition, the mice used in this experiment did not even have immune systems – if they did, and the graft was able to “take” the presence of an immune system would have eventually led to the development of MS… not a cure.
5. Over ¾ of the mice in the treatment group died at the same time as the untreated controls. Only a small percentage of the mice had any benefit – with only four surviving to live normal lifespans.

Having said all of that – this work still represents a stride forward for stem cell research. And it does hold some promise for future research. It represents one of the first times that stem cells have been successfully used to treat a demyalinating disease in the central nervous system. From a methodologic point of view, this is a huge step forward. It is good news that the injected stem cells were able to spread around the brains of these mice and wrap themselves around axons – this holds some hope for MS patients. Initially low success rates are expected in highly technical research like this – so again, I am not too worried about the relatively small percentage of animals helped in this experiment.

What needs to happen next is for someone to generate glial stem cells, not from the brains of aborted fetuses, but from the developing cell mass of an SNT embryo. Done correctly, this procedure could by-pass the need for immune incompetent animals and may open the door for potential treatment of more fully developed animals and humans. Much work still needs to be done – and most of it can be done in animals, thereby delaying the ethical dilemma of using human cells.