Blood, 1 October 2001, Vol. 98, No. 7, pp. 1999-1999
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 cellsmuch 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.
Norman Iscove
The Ontario Cancer
Institute
