Abracadabra: Bone Marrow Cells Turn into Brain Cells

By Ellen Kuwana
Neuroscience for Kids Staff Writer
January 23, 2001

You may have seen the famous performer David Copperfield appear to change a car into an elephant. Neuroscientists appeared no less magical when they transformed blood cells into brain cells. Two research groups reported in the December 1 issue of Science that bone marrow cells can travel to the brain and turn into nerve cells.

Bone marrow, the soft material inside your bones, is composed of at least two types of stem cells. Stem cells are not yet mature and have the ability to become specialized cells. During development, stem cells can become a variety of cell types: bone marrow cells have been shown to become muscle, bone and liver cells. Different signals tell the stem cell what type of cell to become. This process is called differentiation, because the cells are migrating to where they belong and becoming different cell types. Scientists used to believe that once a stem cell became a specialized cell, say a liver cell, that its cell type was unchangeable. Recent work, however, is breaking down this long-held belief.

In order to trace what happens to the transplanted cells, scientist need a marker, something that identifies the transplanted cells from the cells that were already there. Think of it this way: if you released some ants into an antpile and wanted see where they would go, you would need a way to trace their route. For example, if you put red ants into an antpile that housed black ants, it would be easy to see where your red ants went.

The first team of scientists, led by Helen Blau at Stanford University, used adult bone marrow cells that contained a green protein that glows in the dark: green flourescent protein or GFP. The host mouse's own bone marrow cells were destroyed by radiation, so the mouse needed donor bone marrow in order to make the cells that make up blood (similar to people who undergo radiation therapy for cancer, and then need a bone marrow transplant). Adult donor cells were injected into the tail vein of the adult host. One to six months later, when the researchers examined the brains of the mice, they were surprised to find GFP inside brain cells, meaning that these cells had originated from the bone marrow. What's more, these cells in the brain looked like nerve cells and were making proteins that nerve cells make. In other words, the transplanted cells were able to respond to signals in the brain that told them to change into brain cells. Abracadabra...from bone marrow cells to brain cells!

The second team of scientists, led by Eva Mezey of the National Institute of Neurological Disorders and Stroke (NINDS), used a different method to trace the bone marrow cells. They exploited the difference between males and females: males have XY chromosomes and females have XX. The researchers used donor bone marrow cells from adult male mice (XY) and injected the cells into newborn female mice (XX). When examining the brains of the female mice, any cells containing a Y chromosome had to be from the donor cells. Indeed, cells containing Y chromosomes were found in the brain. Although it had been observed before that bone marrow cells could become astrocytes and glial cells ("support"cells in the brain), no one expected a change to nerve cells.

Much more work needs to be done. The bone marrow cells seem to have changed into nerve cells, but are these cells truly nerve cells? They appear to be making proteins that nerve cells make, but this is not definite proof that these cells are acting as nerve cells. Here are some questions that still need answers:
  • Do these cells connect to other nerve cells and send signals?

  • Why don't more of these new cells look like mature nerve cells? Most had short non-branching outgrowths, not the long extensions of mature neurons.

  • What signals make the cells migrate to the brain and what factors guided or allowed the cells to travel to the brain? The donor cells were injected into the bloodstream, so the cells had a long road to reach the brain.

  • How do cells change cell type and what signals are necessary to tell cell A to become cell B? These factors may include growth factors and tropic factors.

  • What variables influence differentiation? For example, how does age of the recipient mouse and the radiation used to kill the host bone marrow cells affect signals that tell cells to migrate.

  • Does this method work in humans? Human cells grow more slowly, and divide less often than mouse cells. This work will be complicated by ethical considerations because research involving cells from human embryos and fetuses is limited. Current guidelines by the National Institutes of Health permit federally funded scientists in the US to work with stem cells from human embryos. The creation of embryos for research purposed is strictly prohibited.
One advantage of this approach as a treatment for disease is that the cells would come from a patient's own body. In other words, a patient's bone marrow cells would be used to make his or her brain cells. Thus, there would be no donor-host incompatibility, such as that sometimes seen in organ transplants where the host's body rejects the foreign tissue. This means that there would be no need for immunosuppression, where drugs are used to quiet the immune system, thus leaving the patient vulnerable to life-endangering infections.

Any step forward in understanding the complicated mechanisms underlying cell differentiation, cell migration, and the various signals that guide these processes is a step towards treatment for diseases characterized by loss of nerve cells. This includes therapies for disorders such as Parkinson's disease, Huntington's disease, and stroke.

References and further information:

  1. Brazelton, T.R., Rossi, F.M.V., Keshet, G.I., Blau, H., "From Marrow to Brain: Expression of Neuronal Phenotypes in Adult Mice," ScienceVol. 290, December 1, 2000, pp.1775-1779.

  2. Mezey, E., Chandross, K.J., Harta, G., Maki, R.A., McKercher, S.R., "Turning Blood into Brain: Cells Bearing Neuronal Antigens Generated In Vivo from Bone Marrow," Science Vol. 290, December 1, 2000, pp. 1779-1782.

  3. Stem Cells: New Excitement, Persistent Questions by G. Vogel

  4. National Institutes of Health Stem Cell Information

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