June 23, 2009
UC Davis opens stem-cell program for horses
Stem-cell therapy: a highly active field
By: Timothy Kirn
For The VIN News Service
Researchers at the University of California, Davis' (UC Davis) recently opened equine stem-cell center expect to collaborate with human stem-cell researchers.
That is because in the clinic veterinary medicine is far ahead of its human counterpart.
While human stem-cell research has been awash in controversy concerning the use of embryonic stem cells, veterinary medicine has quietly forged ahead, using stem cells from adult tissues instead of embryos, harvested from marrow and fat.
Because the stem cells come from the animal being treated, there is no need for governmental approval of the procedures.
The first equine procedure is thought to have been done in 1995, by Douglas J. Herthel, DVM, of the Alamo Pintado Equine Medical Center in Los Olivos, Calif., just north of Santa Barbara. Now there are two companies that offer to process stem cells for veterinarians nationally: Vet-Stem, Inc., of Poway, Calif., and VetCell Bioscience, Inc., a British company that last year began business in North America.
Recently small-animal veterinarians have gotten into the picture, treating dogs and even some cats, for those with the wherewithal. The procedures cost upwards of $3,000.
Herthel, for one, says there is a great need for the UC Davis Regenerative Medical Laboratory, as the new center is known, despite the fact that so many are already performing procedures.
While stem-cell therapy appears to be beneficial, little is known about how and why it produces healing, says Herthel, who is going to be collaborating with the laboratory.
Do injected stem cells incorporate themselves into injured areas and form new tissue? Or do they release cytokines that promote better healing, as much work suggests? Or, do they do both?
“Even though it is being used extensively clinically, there is always the need for more research,” Herthel says. “You have to be able to show how it is working.”
There is no definitive proof that stem-cell therapy works, though many observers describe seemingly miraculous results. There has never been a blinded, controlled clinical trial.
What exists are anecdotal accounts, some laboratory work and a few case series.
Adult mesenchymal stem cells, as the type used are known, might have application in many conditions, but so far therapy is typically of ligament or tendon injuries, osteoarthritis and fractures. Practitioners say the animals that undergo a stem-cell treatment can show marked improvement in just a few weeks, and the improvement continues for a few months.
Thoroughbreds with suspensory ligament injuries return to racing, and some notable horses have won. Dogs that could not jump up on the bed start to frolic like puppies.
In 2001, Herthel reported his results on 100 horses with suspensory ligament injuries treated with injections of stem cells and compared his results with 66 horses that he had treated conventionally. At six months, 84 of the treated horses had returned to soundness and work. Only 11 of the conventionally treated horses became sound and did not reinjure the ligament within a year ( AAEP Proceedings 2001;47:319-21 ).
Herthel says he has been working with a human orthopedist who has treated a patient with an Achilles tendon injury. That patient described having significant pain relief just two days after the procedure.
Vet-Stem has reported on 66 horses with tendon injury treated. The company said that one year after treatment 77 percent were injury-free and had returned to their previous activity. Historically, only half of horses with similar tendon injuries return to full activity, and 40 percent to 50 percent have a reinjury.
VetCell says its data shows a 50-percent reduction in reinjury in race horses followed for three years, and among 82 horses treated and followed for more than one year, 78 percent had returned to full training.
However, as some researchers point out, these are uncontrolled, company-funded case series, and the initial claims, while provocative, should be substantiated in well-designed controlled clinical trials.
Colorado State University (CSU) researchers, David Frisbie, DVM, and John Kisiday, PhD, have reported publicly on 15 horses they have treated. Most were reining horses. Their injuries included subchondral bone cysts, cartilage damage, and torn menisci. They said 10 of the 15 became sound, and returned to their previous activity level in their given discipline, in an average of 78 days.
They have launched a commercial venture based on their early results.
Private practice veterinarians who post on the VIN Message Boards report mixed results with stem-cell therapy. But nobody dismisses it as useless. And some describe dramatic improvements in treated animals.
One said that she treated both stifles in a 60-pound Husky mix, that had undergone a previous cruciate repair. “I think we are 10 months post treatment now,” the veterinarian wrote. “It is pretty impressive really. The owner has stopped all meds, the dog is doing well.”
Patrice Mich, DVM, a post doctoral fellow in integrative pain management at CSU, has been doing procedures using Vet-Stem since the fall. “My cases have done well and I will continue to recommend stem cells in carefully selected, properly diagnosed cases,” she says.
The expansion of stem-cell therapy from horses to dogs has occurred fairly rapidly, and it was unexpected, says Julie Ryan Johnson, DVM, the director of sales and marketing for Vet-Stem.
She says the company never anticipated much demand in the canine market due to the cost, and so started out focusing on the equine market. But then small-animal veterinarians began coming to them, asking to be trained in the procedure and to have their material processed. Most had been pushed by dog owners, she says.
“A lot of this has been driven by the client,” she says.
Ryan Johnson says the company began offering services to small-animal veterinarians last year, and that business has grown fast. Within three months, the number of small-animal veterinarians using the service equaled the number of equine veterinarians (though, of course, there are a lot more small-animal veterinarians, she adds). Currently, about 60 percent of the more than 1,500 veterinarians trained in the procedure by the company treat small animals, she says.
UC Davis researchers will be using stem-cells harvested from bone marrow, retrieved from the sternum. Vet-Stem holds a U.S. patent on stem-cells harvested from fat. That will put the laboratory’s research in the center of a current debate, says Sean Owens, DVM, an assistant professor of clinical pathology and the new director of the Regenerative Medicine Laboratory.
Some say marrow is a better source of stem-cells because they can be cultured and the population grown into a larger number of cells per treatment infection. It might be that there is a critical number of cells that need to be injected for optimum results, perhaps 10 million or more per milliliter injection.
Others have suggested that fat is the better source. It naturally has a greater number of stem cells per sample of tissue. Culturing the cells might be detrimental, since it is possible that when the cells are grown there is selection among the stem cells that occurs, resulting in a population that does not contain every type of mesenchymal stem cell there is when the culturing was started. It is not known if this occurs, or whether it is important, but it is a possibility.
And, since it is not known exactly how stem cells spur repair, it is not know whether fat- or marrow-derived cells have all of the same advantages.
Frisbie’s CSU group, which is working to compare the two, recently reported on a comparison of their ability to prompt chondrogenesis. Their study was done in vivo, but it suggested that the stem cells derived from bone-marrow produced greater activity than did fat-derived cells ( J. Orthop. Res. 2008;26:322-31 ).
There are other possible issues as well. Vet-Stem maintains treatment is better when done soon after injury, which might preclude waiting two or three weeks for culturing. Those who use marrow say the incision used to collect fat cells is more likely to lead to problems than the needle aspiration used to collect marrow. And, many owners of competitive horses do not want their animal to have a scar that advertises the fact that it has had a stem-cell procedure.
“At the end of the day, they are both a great source for stem cells,” says Ryan Johnson.
With its new laboratory, UC Davis becomes one of at least four centers in this country that has a concerted, veterinary stem-cell program. The others include CSU, University of Pennsylvania and Cornell University.
Owens says the impetus for the stem-cell lab came from a retired, Bay Area executive who owns reining horses. The executive, Richard Randall, who was a real estate developer before retiring, gave $425,000 to get the school started in stem-cell therapy in 2008.
The school also entered into an agreement with a local, Northern California-based company named ThermoGenesis to use and help develop its stem-cell processing equipment.
But the laboratory technicians and others who were involved in the work were quickly overwhelmed with demand, Owens said.
So the school decided to expand the effort, and with an additional $2.5-million grant secured from Randall, the laboratory was born. It has 10 staff members and will train at least three graduate students at a time.
The human researcher that Owens expects to work most closely with is Jan Nolta, PhD, of the UC Davis Medical Center in Sacramento. The Medical Center recently initiated a plan to build a $62-million institute to conduct stem-cell research, including clinical trials. In June, a group there reported that they were able to grow functional blood vessels in mice with ischemia using human adult stem cells.
Coincidentally, Nolta used to be a barrel rider.
In fact, human medicine is already following veterinary stem-cell practice. The parent company of VetCell has announced that, based on the work with horses, it is conducting a trial of stem-cell treatment for Achilles tendon rupture. Last fall, noting the experience of veterinary medicine, the National Institutes of Health announced that it is opening a bone-marrow stem-cell transplant program in the National Institute for Arthritis and Musculoskeletal and Skin Disease.
Owens says the potential for their research efforts is tremendous. He thinks stem-cell therapy works, but the possibilities have not been exhausted and improvements can be made.
He draws an analogy to fire. Fire can warm a cave. But it can also take a rocket to the moon, he says.
Stem cells “are probably not as effective as we would like them to be right now,” he says. “We are still just trying to learn their language. But five years from now, what we are doing today will look like we were using rocks for hammers.”
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