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Celling Brain Repair

Cells deep within the bone may one day yield a readily available source of neurons to treat Parkinson’s disease, stroke and other neurodegenerative disorders, a USF study found.

The study, which was published in the August issue of the journal Experimental Neurology, demonstrated that both mouse and human stem cells that produce bone marrow can be reprogrammed in the laboratory to become immature nerve cells.

“It’s striking that we can generate new kinds of cells from deep within the bone, including cells with the potential to become neurons for brain repair,” says Dr. Juan Sanchez-Ramos, the Helen Ellis Professor in Parkinson’s Disease Research at USF and lead investigator for the study.

Neuroscientists continue to seek alternatives to human embryonic neurons as a source of therapeutic cells for brain repair, according to Paul Sanberg, director of the USF Neurosciences Program and a study co-author. Bone marrow stem cells offer several potential advantages, he said. The cells are readily accessible, since they are already collected from bone marrow donors for certain cancer treatments. And stem cells can be extracted from a patient’s own bone marrow, so they are less likely to be rejected than neural cells coming from other sources.

Stem cells are primitive cells in developing embryos that can multiply indefinitely, migrate to different parts of the body and develop into any kind of tissue. Bone marrow retains the ability to generate stem cells throughout life. Left to their own devices, these bone marrow stem cells typically give rise to bone, blood and cartilage.

But the USF researchers found that when a certain type of bone marrow stem cell -- a stromal cell -- is cultured in the laboratory with retinoic acid and growth factor, the cells lose their bone marrow characteristics and begin to resemble immature neurons or glial cells -- the supporting cells of the brain. They also have several neural proteins.

Furthermore, when these transformed bone marrow cells were combined with fetal rat brain tissue in a petri dish, the number of neuron-like cells doubled. “This suggests that the environment in which a stem cell is raised is critical in determining what type of cell it will become,” Sanchez-Ramos says.

Last year, Italian and Canadian scientists reported that neural stem cells from mice changed their identities and began to make bone marrow when injected into other mice whose bone marrow stem cells had been virtually destroyed by radiation. Sanchez-Ramos says this work suggests that the reverse-cueing bone marrow stem cells to make brain tissue -- is possible. “It’s a radical approach, but not without precedent,” he says.

Sanchez-Ramos stresses that more extensive studies are needed to determine whether the bone marrow-derived stem cells triggered to resemble early nerve cells can actually develop into functioning neurons. The USF researchers
have begun cloning the stem cells and transplanting them into an animal model for stroke to see if they can replace damaged brain tissue.

The study was funded by the National Parkinson Foundation, a Veteran’s Administration Merit Review Grant, Layton BioScience and the Helen E. Ellis Research Endowment at USF. Layton BioScience has licensed the rights to this stem cell technology and is developing it for clinical use.

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