Scientists Compare Pluripotent Cell Isolation and Properties

Nature, September 8, 2008

"Potency" is one of the most important properties of a stem cell, and a measure of the cell's ability to differentiate into various types of tissue. As one of the highest forms of potency, second only to totipotency, "pluripotency" is a coveted feature reserved only for embryonic stem cells and iPS (induced pluripotent stem) cells. Safety and efficacy are also of the utmost importance, however, and pluripotency is well known to be associated with specific risks, especially the formation of teratomas, which are a unique type of tumor.

In the latest issue of the journal Nature, two leading scientists in the stem cell field, Drs. Rudolf Jaenish and Christopher Lengner, both of the Massachusetts Institute of Technology, offer a striking visual illustration that compares the pluripotency of embryonic stem cells with the pluripotency of laboratory-generated cells that are derived from non-embryonic sources, such as the iPS (induced pluripotent stem) cells that are reprogrammed from adult skin cells.

Embryonic stem cells are known not only for the ethical dilemmas that they present, but also for a long list of scientific problems which include difficulty of isolation, biological and chemical contamination, genetic mutation, a lack of controllability during differentiation and, by definition, the ability to form those very specific types of tumors which are known as teratomas. Indeed, as depicted in Drs. Jaenish's and Lengner's illustration, teratoma formation remains one of the universally accepted criteria by which pluripotency is defined and empirically determined, even for cells which are not of embryonic origin, such as the iPS cells. Created through such techniques as nuclear transfer, genetic reprogramming and cellular fusion, ordinary adult somatic cells which are not stem cells have been induced to behave with a pluripotency that resembles that of embryonic stem cells, but which circumvents the ethical controversy surrounding embryonic stem cells, by avoiding the use of embryos altogether. These cells, such as the iPS cells, may have solved the ethical controversy, by entirely circumventing the need for embryonic stem cells, but these newly derived pluripotent cells do not solve the medical problems and risks that are associated with teratoma formation, since such cells, by definition, still cause the formation of teratomas and this is still how pluripotency is defined and identified. If a cell forms a teratoma, then it is recognized to be a pluripotent stem cell - whether of embryonic origin or of non-embryonic origin, such as the iPS cells.

Adult stem cells, by contrast, do not form teratomas since they are not pluripotent but instead are, at best, "multipotent", and as such are well understood to be "lineage-restricted" in their differentiation ability. While such a lack of pluripotency has, in the past, been erroneously seen as an undesirable feature of adult stem cells, it is now recognized as being highly advantageous for a number of reasons which include greater controllability in the differentiation process and no risk of teratoma formation, among other advantages of adult stem cells.

The entire fields of tissue engineering and regenerative medicine are founded upon properties of cellular potency, but not all stem cells are created equal, and a wide spectrum exists across which their properties may be ranked. The specially featured illustration by Drs. Jaenish and Lengner in the latest issue of Nature is already recognized as offering a new and updated set of guidelines for scientists in the field, and a free copy of the illustration may be downloaded at the journal's website, www.nature.com.