Feature articles
Argonne Update

Serendipity in lab turns
blood into stem cells

by Amy Kile

With a serendipitous start, Argonne biologists have found a source of pluripotent stem cells that is as close as the human blood stream.

Previously believed to be found only in bone marrow, which is difficult to collect, and embryonic cells, which raise ethical concerns, these flexible stem cells are rare. But with Argonne's findings, published in the March 4, 2003, Proceedings of the National Academy of Sciences, stem cells may soon be plentiful and easy to harvest.

Images of blood monocytes (left) and similar cells converted into stem cells (right).

BLOOD TO STEM CELLS — Blood cells can be transformed into stem cells. These images show peripheral blood monocytes. At left are freshly isolated, untreated cells. At right, the image shows similar cells 14 days after treatment, when they have morphed into pluripotent stem cells.

These cells are termed pluripotent because they can morph into many specific body tissue cells. They are the research tools scientists and doctors need to study and treat diseases from cancer to Alzheimer's. Patients with spinal cord injuries, Parkinson's disease, stroke and heart disease will also benefit from this research.

Currently, donated organs and tissues are used to replace destroyed tissues, but donor demand exceeds supply. Stem cells induced to form other cell types would make a renewable source of new cells to treat diseases with transplantation or cell replacement therapy.

For example, if stem cells are made to generate healthy heart muscle cells in the laboratory, they could be transplanted into chronic heart disease patients. Because they would come from a patient's own blood supply, the body would not reject the transplanted material, eliminating the need for harsh anti-rejection drugs.

Similarly, stem cells coaxed to form neurons could be transplanted into the body to repair damaged nerve cells. Such a feat could possibly heal spinal cord injuries and treat neurological diseases such as Alzheimer's and Parkinson's disease.

Pluripotent stem cells could be the key to studying the human body from its embryonic stages to maturity, allowing researchers to see what intricate processes occur during both normal and abnormal development.

But until now this flexible type of stem cell was not readily available. Although adult stem cells showed promise in some research areas, embryonic stem cells are more desirable to researchers because they start out unspecialized but can be manipulated into forming cells with specific functions.

Argonne researchers may have found an abundant supply of pluripotent stem cells, which originate from adult rather than from embryonic tissue.

Eliezer Huberman, group leader of gene expression and function at Argonne's Biochip Technology Center, showed that monocytes — immature white blood cells that are precursors to infection fighting cells called macrophages — in the human bloodstream can form pluripotent stem cells.

Stem cell serendipity

Huberman discovered the stem-cell like characteristics of monocytes when Yong Zhao, a postdoctoral fellow working with him in the center, became ill and could not attend the culture plates he was using for another experiment.

Huberman, Zhao and David Glesne, also a biologist in the gene expression and function group, were studying the signals involved as monocytes are converted into macrophages.

They inoculated culture plates with monocytes, supplementing the dish medium with various growth factors — proteins that bind to receptors on specific cells and promote their growth. These growth factors matured the monocytes into macrophages.

When Zhao was ill, a monocyte culture did not receive fresh nutrients. Realizing the error, the biologists worked to salvage any remaining cells. When they viewed them under a microscope, they found that a fraction of the surviving cells had not differentiated into ordinary macrophages.

"We found that some of the surviving cells had morphed into cells that were different than macrophages," said Huberman. "For example, we found that a few of them had the appearance of blood vessel cells, and others of nerve cells."

Upon this discovery, Huberman decided to perform systematic experiments with monocytes to verify the accidental finding.

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