MDA Sponsors Muscle Stem Cell Workshop

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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 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

-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 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.

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