Research Casts Doubt On Circulating Stem Cells

Bone marrow constantly produces stem cells from which, amongother things, the white and red blood corpuscles are formed. The dreamof many scientists is to breed other types of tissue from bonemarrow-derived cells. In recent years a great deal of hype has beengenerated around the idea of a "cellular jack of all trades" -- notleast because some studies gave grounds for hope. Using irradiationtechniques, researchers managed to destroy the bone marrow in mice andreplace it with cells which became green-fluorescent thanks to agenetic addition. A short time later they then discoveredgreen-fluorescent nerve cells in the mice's brains. This appeared tothem to be evidence that the stem cells circulating in the blood couldactually transform themselves into nerve tissue. It looked like thediscovery of a completely new mechanism: the repairing of tissue usingstem cells from the blood stream.

What excited medical scientists most was the idea that thebody had at its disposal a kind of "mobile task force" of repair cells,constantly moving through the body and replacing damaged tissue. Evensevere diseases like Duchenne muscular dystrophy (DMD), which destroysall the body's muscles, appeared to be potentially treatable -- indeed,by the simple means of transplanting healthy bone marrow. For boys, DMDis the second most common hereditary disease. Due to a genetic defect,the muscles fail to produce properly functioning dystrophin, animportant muscle protein. Those affected develop progressive musclewasting. They only have a life expectancy of 15 to 20 years.

"In mice with DMD we have replaced the bone marrow withhealthy marrow marked by a fluorescent gene," explains Bonnphysiologist Professor Dr. Anton Wernig. The hope of the medicalscientists is that the transplanted stem cells will find their waythrough the blood into damaged muscle fibres where they can producefunctioning dystrophin. The Bonn researcher team was in fact able todetect green-fluorescent stem cell nuclei in the muscle fibre forseveral months after the bone marrow transplantation. And, as ProfessorWernig emphasises, "they were found in numbers that would have had tobring a significant improvement to the condition of the muscle." Thenext step was to find out whether the stem cell nuclei were actuallyproducing muscle proteins. Here, the results were negative: "If at all,very few nuclei produced dystrophin -- in any case, far too few toachieve any improvement in the condition." The physiologist concludes,"Although the cells do merge with the defective muscle, we suspect thatthey remain silent and cannot set off the hoped-for 'muscleprogramme'." In other words, the bone marrow-derived cells are notconverted into functioning muscle fibre.

The myth of a circulating jack of all trades

The reason is probably that in nearly all cells released intothe blood from bone marrow many genes are permanently "switched off"and the cells cannot simply be switched back on again. After all, whatcomes from bone marrow is generally blood and not muscle tissue. Thestory of a "jack of all trades" circulating via the blood streamthroughout the body and repairing, wherever needed, any type of tissueis, unfortunately, a myth. In practice their impact is, at best,minimal.

The somatic cells mark genetic traits believe by the body to beno longer needed by sticking a label on them -- a sort of molecular"Don't use!" sign. "We have tried to remove this label by chemicalmeans, too, in an effort to get the nuclei of the bone marrow-derivedcells to start producing muscle proteins again," says Professor Wernig."While we were able to activate dystrophin production in the muscle,the effect was nowhere near the level needed to combat the disease. Butwe shall continue working on this and try to awaken those 'sleepingbeauties', the nuclei."

The Bonn physiologist believes that it is necessary to dampenthe very high expectations held by some colleagues: "In my view, manyof the studies using bone marrow-derived stem cells have so far beeninterpreted over-optimistically." The experiments withgreen-fluorescent nerve cells would seem to be one such case: "The bonemarrow-derived cells have probably migrated from the blood into thebrain where they do not change into nerve cells but blend with theneurones that already exist there." In this case, the presumed stemcells would only have coloured a few brain cells green.