MDA Sponsors Muscle Stem Cell
Workshop
On June 14, MDA sponsored a muscle stem cell workshop as part
of the 2005 FASEB (Federation of American Societies for Experimental
Biology) summer research conference on muscle satellite and
stem cells, held in Tucson, Ariz.
Among the participants at this scientific workshop were several
MDA-funded researchers, including Elizabeth McNally of the University
of Chicago, Lou Kunkel of Harvard University and Children’s
Hospital of Boston, Giulio Cossu of Istituto Scientifico San
Raffaele in Milan, and Brad Olwin, of the University of Colorado.
Several researchers from Europe were also present, including
Gillian Butler-Browne and Marc Fiszman, both at INSERM (Institut
National de la Sante et de la Recherche Medicale) in Paris.
The highlights of the presentation and discussions included
the following:
* If we are to again contemplate cell-based therapy for muscle
disease, we must choose a different type of cell from those used in the “myoblast transfer” trials
of the early 1990s.
It is now known that the cells used at that time were too
far advanced in their development toward becoming muscle (too
“differentiated”), and the vast majority of them
were not able to fuse with existing muscle fibers or form new
fibers in the recipients.
* Findings over the last decade have shown that cells that
give rise to muscle (muscle progenitor cells) go through several
stages of development (differentiation). We will probably want
to choose cells that are not as far along as the myoblasts
we used in earlier trials.
* The good news is that we will not need to enter the
fracas about embryonic stem cells for cell-based treatment of
muscle disease, as these do not appear necessary and
may even be less effective and carry more risks than muscle
precursor cells. (Cell transplantation to repair or regenerate
nerve tissue was not addressed in this forum, but embryonic
stem cells could be of more importance in that context.) There
are non-embryonic stem cells present in muscle and perhaps also
in the bone marrow and blood vessel lining that are probably
better suited to repair and regeneration of muscle.
* The risks of transplanting cells into the heart, even
though this is being tried in a few patients in Europe, are
too great to warrant attempting at this time. The heart
muscle lacks the natural repair mechanism and stem cell populations
that skeletal muscles have and isn’t programmed to take
up new cells in the same way. If the cells were to engraft themselves
in the wrong place or connect to existing cells in the wrong
way, warned cardiologist Elizabeth McNally, the risk of dangerous
or even fatal heart rhythm abnormalities would be very high.
* There are several “down-side risks” to be concerned about even in contemplating skeletal muscle
transplantation. Chief among these is the risk of immunologic
rejection of cells transplanted from one person to
another, along with the risks incurred when a recipient is given
powerful drugs to suppress the immune system. It was noted that
several of these drugs, in addition to their known toxicities,
may also interfere with the survival or engraftment of the transplanted
cells.
Also among the risks are the possibilities that the transplanted
cells could become something other than muscle (such
as bone or fat), or that they could develop malignant
characteristics and form tumors. To overcome these
unacceptable risks, it was suggested that the transplanted cells
be equipped with a “cell suicide” mechanism that can be activated with a drug given to the patient. |
