Biology/physiology of stem-cell therapy
"While provocative, studies documenting cellular transdifferentiation, i.e., the ability of adult stem cells from one tissue
type to form specialized cell types of other tissues, should be carefully reviewed and regarded with some skepticism. Very
few of these studies demonstrate functionality of the terminally differentiated cell type," Fortier cautions.
"There is considerable data regarding cartilage-tissue engineering and some data on tendon regenerative studies. What is lacking
is information on characterization of the cells prior to implantation, and data on survival or function of the transplanted/grafted
cells," Fortier says.
"The most controversy is over what these (injected) stem cells are doing," Garcia-Lopez says. "One of the things I suspect
is happening ... is activation of the neighboring cells. That's a hugely debated part of it. We are not really sure whether
these (injected) cells are already differentiated tissue. We think ... you probably have an activation phenomenon. Some of
the cells within that tissue, whether bone, tendon or ligament, likely create more of their own cells, with the assistance
of the growth factors injected with the stem cells."
"One of the areas we are interested in is trying to understand whether stem cells injected into tissues actually remain in
those tissues and can be traced," Peroni says. "So if one can follow them through time and verify that they're not removed
and not destroyed by the local environment of the wound, etc., it would make you believe they are actually doing something.
It would be disappointing if we were not able to find a trace (of them) once they are injected in a tissue."
To trace what happens to the stem cells, Peroni and his group are doing preliminary work with "markers" — specific protein-expressing
genes placed within the cells so that researchers later can observe whether the proteins are expressed in the tissues.
Bone-producing proteins are of particular interest. These are thought to be useful to expedite new bone formation — for fracture
healing and joint fusion, for instance.
"I've used them with pretty decent luck on horses that have required joint-fusion procedures, such as cases of advanced osteoarthritis
of the small hock joints," Peroni says.
The lower joints of the hock often are affected by arthritis that is unresponsive to traditional treatment. "One of the things
they do for those horses is surgically fuse those joints by arthrodesis. In horses we treated recently with the addition of
stem cells, we were impressed with the amount of bone turnover," Peroni says.
Researchers also are exploring the use of other markers, such as fluorescent dyes, to follow cell activity.
The University of Georgia researchers are interested in tracing marked cells during laminitis treatment, but there's a problem
with that, Peroni says.
"The problem is that there is no practical way to put stem cells in laminar tissue because it is trapped between the hoof
capsule and the coffin bone; we don't have direct access to it," he explains.
"They're trying to take advantage of a feature of MSCs called patho-tropism," Peroni says. "These cells apparently can hone
in to a site of injury. If so, it would be interesting to be able to administer the cells to the horse essentially rather
than to the foot and watch them target the specific area of injury. It's a bit of a long shot but something that we're trying
to explore," Peroni says.