Direct Conversion Challenges Embryonic Stem Cell Research

Bioethics   |   Rebecca Taylor   |   Sep 20, 2011   |   11:58AM   |   Washington, DC

The Scientist has a great article called “Skipping Pluripotency.”  What is pluripotency?  Pluripotent is a term used to describe a cell that is undifferentiated.  A pluripotent cell can become most or all of the cell types in the body. Pluripotent stem cells come from embryos, either made from IVF or cloning, that are ripped apart for the stem cell mass inside. Recently, scientists have been able to induce pluripotency.  They are able to take a fully differentiated cell like a skin cell and reprogram it back to pluripotency.  These are called induced pluripotent stem cells or iPSCs.

So why is pluripotency desirable?  Well, it was thought that best way to get any kind of cell that was needed for therapy was to start with a pluripotent cell and differentiate it into the cell type of interest.  Scientists envisioned taking pluripotent stem cells and making them into any kind of cell they wanted.

The researchers profiled in “Skipping Pluripotency” are doing just that and skipping pluripotency altogether.  They are taking one differentiated cell, like a skin cell, and turning it directly into another differentiated cell, like a neuron.

Why are researchers “skipping pluripotency?”  Because the undifferentiated nature of pluripotent stem cells makes them unpredictable and prone to causing tumors.  To use pluripotent stem cells to treat patients, researchers would have to take pluripotent cells and differentiate them into the cells needed.  But if any of these cells retain their pluripotency, they may develop into tumors.  This is exactly the reason embryonic stem cells are known to cause tumors in animal models.

Skipping pluripotency reduces the risk of tumor formation which means these kinds of cells made by direct conversion are not only easier to make but also may be safer for use in patients.  From “Skipping Pluripotency:”

The discovery of induced pluripotent stem cells (iPSC) in 2006 opened the door to promising research and therapeutic techniques, such as the generation of disease models and the potential to replace cells damaged by neurodegenerative diseases like Parkinson’s. Derived from fetal or adult cells, iPSC strategies avoided the ethical issues surrounding embryonic stem cells. But they retained one critical drawback—the propensity for tumor formation. In the last 18 months, however, researchers have discovered a new reprogramming technique that could avoid that problem altogether: the direct conversion of one differentiated cell type to another.

“Skipping pluripotency provides you the opportunity to avoid any possible tumorigenic source of cells,” says molecular biologist Vania Broccoli of the Stem Cells and Neurogenesis Unit at the San Raffaele Scientific Institute in Italy. “We believe that we are providing now a new source of cells which have an improved potential for these treatments and can be translated in the human systems.”

So far the scientists are only using direct conversion in mouse cells and only in the lab.  They are working to make sure that directly converted cells work inside the mouse as well. Researhcers also need to find safer ways to accomplish the direct conversion before using this technique clinically, but direct conversion holds great promise.

The important thing to take home is that these scientists want to continue developing a technique to skip pluripotency altogether.  This challenges the idea that pluripotent stem cells are the most desirable in stem cell research.  And since pluripotent stem cells are the kind that you get by ripping open embryos, this direct conversion technique further challenges the idea that stem cell research needs embryos at all. Note: Rebecca Taylor is a clinical laboratory specialist in molecular biology, and a practicing pro-life Catholic who writes at the bioethics blog Mary Meets Dolly. She has been writing and speaking about Catholicism and biotechnology for five years and has been interviewed on EWTN radio on topics from stem cell research and cloning to voting pro-life. Taylor has a B.S. in Biochemistry from University of San Francisco with a national certification in clinical Molecular Biology MB (ASCP).