Is plasticity here to stay?

A short while ago, tissue stem cells in adults were thought to be restricted to generating only the kinds of cells typical of the originating system. For example, neural stem cells would make only neuronal progeny, and hematopoietic stem cells would make only hematopoietic progeny. This tidy state of mind ended when recent reports suggested dramatically otherwise. Bone marrow populations were shown to generate a variety of nonhematopoietic cells in connective tissue and neuronal and epithelial lineages. Conversely, cells from the nervous system and from skeletal muscle turned out to generate hematopoietic progeny. If stem cells of any type could be reprogrammed by exposure to environments other than those of their original tissues, novel and exciting therapeutic opportunities would become available. Thus the current buzz called “stem cell plasticity.”

It was, however, inevitable that the initial euphoria would be followed by morecritical evaluation of the evidence and experimental tests. The study from Kawada and Ogawa (page 2008) describes one such test, addressing the observations that precursor cells isolated from skeletal muscle can reconstitute the hematopoietic tissues of irradiated mice. From the beginning, there were 2 ways to explain the observation. One of these invokes plasticity: stem cells normally generating muscle progeny can be persuaded to make hematopoietic progeny. Proof of this proposition would require clonal evidence not offered with the original reports. A second explanation would be coexistence in muscle tissue of both muscle stem cells and hematopoietic stem cells, since marrow stem cells are known to circulate. Kawada and Ogawa now demonstrate that, following reconstitution of irradiated mice with genetically marked marrow, stem cells in muscle that reconstitute hematopoiesis are all of donor marrow origin. The result establishes the existence of marrow-to-muscle trafficking of stem cells and thus makes the second explanation—coexistence in muscle of distinct stem cells—much the safer bet.

The scientific foundations of stem cell plasticity are not conclusive, and additional challenges based on more compelling experimental designs are likely under way. Stay tuned.