Researchers Discover Method Of Removing Potential Tumor-Causing Stem Cells From Cells Developed For Use In Medical Treatments

Effective tricks for separating stem cells from other types are essential for many emerging medical treatments. These treatment approaches begin with researchers inducing stem cells to take specific forms, or differentiate, for instance into nerve cells. These differentiated cells might then be used to repair a spinal cord injury. Other cells might enable a diabetic's body to produce adequate insulin.

A key problem is that in the differentiation process, at least some stem cells inevitably remain in their undifferentiated, or pluripotent, state. These cells can grow to form tumors in patients if injected along with differentiated cells, a concern that has already led the US Food and Drug Administration (FDA) to delay clinical trials for promising stem cell-based therapies.

So far almost all attempts at purification have focused on developing antibodies—immune system attack cells—that can remove or destroy stem cells in mixtures. But this approach has had shortcomings. Effective antibodies are difficult and expensive to develop, and their use in medical therapies raises safety issues because they are produced in animals.

Recently researchers have begun experimenting with chip-based tools known as lectin arrays. At various points on these devices, plant-produced proteins called lectins are attached. These lectins bind with specific sugars including some found on the surface of cells.

Working in the lab with cellular components, rather than whole cells, researchers at Scripps Research Institute, led by Professor of Developmental Neurobiology Jeanne Loring, found that specific combinations of sugars and proteins known as glycoproteins on stem cells reliably bind to certain lectins. They were then able to exploit this connection to purify cell mixtures.

After identifying the lectin that bound best with stem cells, the group took the work to the next level to show that they could actually separate out stem cells. To accomplish this, they first attached the lectin to tiny beads. Then they exposed these beads to mixtures of stem cells along with non-stem cells.

The researchers used a range of different types of both embryonic stem cells and induced pluripotent cells, which are embryonic stem cell-like cells that are produced by inserting certain genes into skin cells. They included cell lines from both Scripps Research and the labs of their collaborators in Japan and the United States.

In every case, the researchers found that the stem cells bound remarkably well to the beads, while the cells that washed past were almost all non-stem cells.

Possible uses for the new technique are essentially as numerous as those for stem cells themselves. Lectin purification could be used with any of a huge range of therapies currently in development. In addition to low cost and reliability, the lectins used are plant products, so they do not introduce the type of safety concerns that could arise from using antibodies that are produced by animal cells.

The Loring team is also working to identify different binding patterns that would allow them to similarly purify mixtures of specific types of non-stem cells. "In theory, this should allow us to pull any cell type out of any mixture," she said of the basic lectin technique.

At the more basic research level, because all the different stem cell lines from both humans and animals seem to produce similar glycoproteins binding to the lectins, it is possible these glycoproteins infer some basic qualities fundamental to the pluripotent state. Loring and her colleagues are exploring this possibility in hopes of better understanding stem cells' still mysterious abilities to transform into any type of cell. "We may have uncovered something really fundamental about pluripotency," said Loring.

Adapted from the Scripps Research Institute announcement.