Let's say you urgently need some all-purpose, homegrown stem cells to treat a medical condition. What if you could simply draw a few drops of your own blood and refine those stem cells for your personal use?

That's the futuristic picture painted by a paper in the latest Proceedings of the National Academy of Sciences, (PNAS), released online today, Feb. 24, 2003. It's titled: "A human peripheral blood monocyte-derived subset acts as pluripotent stem cells."

The paper's senior author is cell biologist and molecular geneticist Eliezer Huberman at the Argonne National Laboratory's Biochip Biotechnology Center, affiliated with the University of Chicago.

"We found a new class of potential stem cells," Huberman told BioWorld Today, "which we can expand. These cells are pluripotent; they can develop into a variety of cell types, including neuronal, liver, endothelial, macrophages and lymphocytes. And this is just the beginning of our studies.

"The other thing," Huberman continued, "is the fact that our cells resemble some research done recently by other investigators. They found that those cells were able to repopulate, or at least populate, certain human tissues. So potentially our cell system will be useful for future transplantation studies. And what's unique about it is that we can expand their number, and also maintain them in a frozen state. One can get these cells from an average person's circulation, freeze them down, because it's easy to get at them, and have them readily ready for potential future use."

Counting The Ways To Stem Cell Novelty

Huberman counted the novelties he found: "One, a subset of known cells called monocytes. Two, that we can expand them. And three, we showed without any doubt, on a single-cell level, that these monocytes are really pluripotent stem cells. Subsequent studies, we hope, will confirm the implication that they can be used in future transplantation - which would circumvent graft rejection - or in the case of neuronal damage, Alzheimer's disease and cancer patients.

"We should be able to transplant them," Huberman speculated, "because our cells will be expanded, differentiated as needed and converted into neuronal and other tissue types. Therefore we will be able to inject these differentiated cells into the appropriate patient - the same individual who has a need for them. And," he pointed out, "you can have cases of people who develop later in life ailments that involve damaged cells - for example Parkinson's disease. For many years these individuals were healthy as young people, indicating that their neurons have a potential to function normally. Perhaps we will be able to prolong the healthy periods enjoyed by these patients by injecting them with new neurons."

He defined Argonne's patent-pending technology as "a way to keep the subset of these monocytes, expand them, then induce them to mature with specific growth factors along different cell lineages."

Here's how Huberman characterized his key monocytes in the teeming population of human blood cells: "The blood is composed of different cell types," he recounted, "of which one component is of course the red blood cells. The other ones are leukocytes, the white blood cells. These divide into different subsets - mainly lymphocytes, granulocytes and monocytes - the smallest subset.

"These monocytes differentiate and mature into macrophages. Their function is to defend the body as an initial defense mechanism against invading foreign organisms by eating them up. Macrophages also produce a lot of growth factors, and present antigens to antibody-producing cells. Our studies entail use of a model cell system for deciphering the signaling steps that lead to conversion of progenitor cells into macrophages. And to confirm it in the real world we went to normal blood monocytes. We had a culture used for other purposes," Huberman recounted, "and we noticed the culture developed a subpopulation that spontaneously manifested cell types with different characteristics, namely, cells that looked to us as neuronal, epithelial, etc.

"Then we started to perform controlled experiments to see if we could really induce these cell types. We then turned to clonal analysis," Huberman recalled. "We isolated single cells from the monocyte subsets, grew up a population of them, and then tested whether the progeny of the single cells can differentiate into different lineages. And they could. Which proves that clonal analysis is the best way to show that a cell is truly pluripotent.

"It then became apparent to us that these monocyte stem cells could serve as alternates to embryonic stem cells. Since ESCs raise legal and ethical questions, we are getting the monocytes solely from adults - consenting adults - for their own medical benefit. I presume that this will circumvent some of those political problems. Also, because you never know where the future leads, and the payoff comes from."

Mice Take Over Disease-Modeling Gigs

"Our ongoing work is to see if we can develop a number of other cell lineages. We want to move now from the human to the model system, like a mouse, and see whether we can with these cells help to alleviate clinical symptoms of a variety of diseases that mice model. We are hoping to start experimenting with mice in the near future.

"There is a significant number of human disease models," Huberman observed, "and we would like to see whether with these stem cells we will be able to cure, or at least help alleviate, some of the major symptoms. These mice will represent in vivo preclinical experiments. When that is finished, we'll go back to human experiments. Hopefully we or other people will do that. And I would expect that our paper will entice a variety of other labs to go in this direction. My post-doc and I are co-inventors of a pending patent application," Huberman concluded, "based on the title of our journal article."