Stem cells in theory & practice

Veterinarians treating horses, dogs, cats with stem cells as research continues
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When Adair had an episode of severe laminitis, the choice was between euthanasia and an attempt to treat the condition with stem cells.

The 1,700-pound horse, an Irish Draught Cross, had previously been given to Drs. Christopher R. and Mindy J. Johnson because they had the expertise to help control the chronic forelimb laminitis the horse had.

Radiographs of Adair's left front hoof
Dr. Christopher R. Johnson of Versailles, Ky., injected stem cells into the front hooves of his horse, Adair, early last year as an attempt to treat severe laminitis. Radiographs of the left front hoof reveal the extent of hoof growth between January and May 2010.

In early 2010, the condition became worse. Dr. Christopher Johnson, a partner at Woodford Equine Hospital in Versailles, Ky., tried all the traditional treatments before injecting stem cells into the horse's front hooves.

In 48 hours, Adair appeared to be in less pain. In six weeks, his hooves grew back about halfway. He's alive today.

Geoffrey the Airedale developed osteoarthritis about two and a half years ago at the age of 9. His owner, Arlene Rose of Portland, Ore., did not want to treat him with nonsteroidal anti-inflammatory drugs because of a previous adverse reaction.

As a result, Rose sought out a veterinarian with experience using stem cells to treat arthritis in dogs. Dr. Scott B. Gustafson of VCA Raleigh Hills Animal Hospital in Portland injected stem cells into both of the dog's hips and administered another dose of stem cells intravenously. Geoffrey has had two additional treatments since.

"He's in a lot better shape than he was, I'm convinced of that," Rose said.

Many veterinarians in private practice have been using adult stem cells from fat, bone marrow, and other tissues as a promising treatment for orthopedic conditions and other health issues in horses, dogs, and the occasional cat. These stem cells can differentiate into many types of cells, including bone and cartilage cells.

Probably the most common approach to the treatment is to collect fat or bone marrow from an animal, send the sample to a laboratory for processing, and then inject the stem cells into the animal. The cost to clients is in the $2,000 to $3,000 range.

The anecdotal evidence for stem cells as a therapy is compelling, but research is still under way to establish the efficacy of the treatment—and the mechanisms of action. The effect of stem cells on cellular signaling could be as important as their potential to rebuild tissue.

Some researchers hesitate even to refer to these cells as stem cells because no one has proved the cells have the ability inside animals, rather than in the laboratory, to differentiate into other cell types.

"We've moved forward so quickly that what we need to do now is put the science underneath," said Dr. Sean D. Owens, director of the Regenerative Medicine Laboratory at the University of California-Davis School of Veterinary Medicine. "Knowing that information will allow us to better craft the therapies to meet the end needs."

Future regulation is another source of uncertainty for the use of stem cells in veterinary medicine. To date, no federal agency has approved or blocked the use of stem cells as a treatment for any condition in animals.

Stem cells in practice

Dr. Douglas J. Herthel, founder of Alamo Pintado Equine Medical Center in Los Olivos, Calif., was one of the first practitioners to use stem cells. Back in 1995, he started using stem cells from bone marrow to treat ligament and tendon injuries in horses. The stem cells seemed to promote healing, so he began to use them for other conditions.

A recent dramatic case was a donkey that became quadriplegic after an injury to its spinal cord, then recovered following treatment with stem cells. Dr. Herthel speaks even more enthusiastically about trying stem cells as an experimental treatment for common equine health issues such as laminitis.

"It's certainly an exciting time to be in the veterinary field," Dr. Herthel said. "You're talking about potential cures for things, rather than just palliation. And you're also talking about maybe less pharmacological use."

Dr. Johnson, Adair's owner, started using stem cells in 2001 to treat tendinitis in racehorses.

"The funny thing about science or lack thereof in clinical practice is you try something for what has historically not been an easy problem to fix, and you have some limited success, and you carry on," Dr. Johnson said.

His equine hospital now offers injections of stem cells from fat or bone marrow as a treatment for a number of orthopedic conditions, including arthritis, when patients do not respond well to traditional treatments.

Some private practitioners process stem cells in-house, including Dr. Herthel. In Adair's case, Dr. Herthel's clinic donated stem cells from another horse for the experimental treatment.

Many practitioners send tissue samples to Vet-Stem Inc., university laboratories, or other laboratories for processing. Recently, MediVet America introduced kits for practitioners to process stem cells in-house.

Dr. Robert J. Harman, Vet-Stem's chief executive officer, said his company has processed stem cells from fat samples for about 8,000 patients since starting in 2004. About 4,000 veterinarians have completed the Vet-Stem credentialing course on stem cells as a therapy.

"Once they've been through the course, most people are pretty strong believers that this has a place in veterinary medicine," Dr. Harman said.

Vet-Stem compiles case studies and has sponsored some clinical trials to compile data about the efficacy of injecting stem cells from fat for various conditions, Dr. Harman said. One of the trials was a blinded study that found improvements in clinical signs of arthritis in dogs that received an injection of stem cells, compared with dogs that received a placebo.

About half of Vet-Stem patients are horses, with the other half being dogs and a few cats. Most of the horses are receiving stem cells for treatment of tendon and ligament injuries, whereas 90 percent of the dogs are receiving them for treatment of arthritis.

Dr. Gustafson performs a laparoscopic procedure on Geoffrey
Dr. Scott B. Gustafson of Portland, Ore., performs a laparoscopic procedure on a dog, Geoffrey, to collect a fat sample. Dr. Gustafson later used stem cells from the fat as a treatment for Geoffrey's arthritis.

Dr. Gustafson, Geoffrey's veterinarian, lectures for Vet-Stem and uses stem cells from fat to treat dogs for orthopedic injuries as well as arthritis.

"We see a fair number of canine athletes, especially the agility dogs," he said. "We also see a number of dogs that are just household pets that have a real tough condition. The family loves them, and they want to do the best thing for them."

Most of the clients who pursue treatment with stem cells believe that their dogs improve as a result, Dr. Gustafson said.

Dr. Gustafson's clinic recently purchased a pressure-sensitive mat as an objective way to assess lameness before and after treatment with stem cells. He said the clinic also is planning to conduct a prospective study comparing stem cells with other treatments for orthopedic conditions.

Stem cells in theory

Some veterinarians see a need for more caution in the use of stem cells.

Among them is Dr. Brennen A. McKenzie of Adobe Animal Hospital in Los Altos, Calif., president-elect of the Evidence-Based Veterinary Medicine Association and author of the SkeptVet blog. The EBVMA has no position on stem cells, but Dr. McKenzie personally believes that the evidence of efficacy is preliminary.

"We get very excited when a new therapy is on the horizon," Dr. McKenzie said. "We have to hold ourselves back sometimes from plowing ahead."

Dr. McKenzie thinks the use of stem cells is a promising avenue for therapy but that the evidence of efficacy and safety is inadequate to justify the expensive treatment in most cases. He would prefer for clinics to offer stem cells as a truly experimental treatment in formal clinical trials.

Researchers at veterinary colleges continue to study stem cells, trying to tease out whether they work as a treatment for various conditions in animals—and how.

One of the few researchers studying stem cells in cats is Dr. Jessica M. Quimby, a fellow at the Colorado State University College of Veterinary Medicine & Biomedical Sciences. Her group has created a bank of stem cells from the fat of healthy cats. Now the group is studying the anti-inflammatory aspects of stem cells in the treatment of chronic kidney disease in cats.

Colby receives stem cell treatment
Colby receives an injection of stem cells as part of a study of their effect on kidney disease in cats at Colorado State University College of Veterinary Medicine & Biomedical Sciences.

"If these cells will decrease inflammation within the kidney, which leads to scarring, then perhaps we can slow down the progression of kidney disease," Dr. Quimby said.

Cat owners frequently contact Dr. Quimby asking whether stem cells could cure their cat's chronic kidney disease, and she has to tell them that the treatment for this condition is palliative and remains experimental.

Dr. Quimby's group is about to start a study of stem cells as a treatment for inflammatory bowel disease in cats.

One of the many researchers studying stem cells in horses is Dr. Thomas G. Koch, an adjunct professor at the University of Guelph Ontario Veterinary College and associate professor at Aarhus University in Denmark.

Dr. Koch is studying the use of stem cells, mostly from umbilical cord blood, as a treatment to improve cartilage repair in horses. His group is trying to determine whether the stem cells have a therapeutic effect and, if so, whether the cells become part of the repaired tissue or influence other cells to do the repair.

"The thinking is basically that we need to know more about the cells, because if we just jump ahead and apply it in the horse, we don't really know what we're putting in," Dr. Koch said. "So it's going to be very difficult to evaluate the treatment outcome and to come up with standardized, reproducible therapies."

Stem cells in the future

A new organization, the North American Veterinary Regenerative Medicine Association, is seeking to act as a clearinghouse of information on stem cells in veterinary medicine, said Dr. Owens, director of the UC-Davis Regenerative Medicine Laboratory and NAVRMA secretary-treasurer.

Dr. Owens has received e-mail from hundreds of practitioners, researchers, and others who want to be NAVRMA members. The first official meeting of NAVRMA will be in June, he said, and the plan is to create standing committees to address subjects such as clinical trials and regulatory affairs.

The Food and Drug Administration and the Department of Agriculture have the authority to regulate the use of stem cells in veterinary medicine, according to a June 1, 2008, JAVMA article on "Regulatory considerations related to stem cell treatment in horses" from Kirkpatrick & Lockhart Preston Gates Ellis LLP in Washington, D.C.

The FDA has promulgated regulations on stem cells in human medicine, but neither the FDA nor the USDA has promulgated regulations specific to stem cells in veterinary medicine. The agencies might approach the use of stem cells from an animal's own tissues differently than the use of stem cells from another animal, according to the JAVMA article.

So far, the FDA has not approved any uses of stem cells in humans, beyond the long-standing procedure of transplanting bone marrow that contains stem cells. Some treatments are in clinical trials, however.