Regenerative medicine technology in humans and animals is advancing at a much faster pace than most of us realize. It has offered hope to thousands of humans suffering from diseases and injuries that destroy or damage vital cells. In animals, much of the research has been focused on orthopedic injuries in horses and dogs: bone fractures, arthritis, and tendon and ligament injuries. There have been numerous clinical trials of stem cell therapy in these animals and the results have been quite encouraging. To this end, The University of California, Davis, Center for Equine Health has initiated a collaborative five-year research study to enhance our understanding of the behavior of stem cells for repairing bone, tendon, and ligament injuries in horses. It is hoped that the knowledge and experience gained from treating horses in these areas will provide sufficient knowledge to not only establish scientifically verified treatment protocols but also support the translation of this technology into the human field.

What is Regenerative Medicine?

Regenerative medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to injury, disease, age or congenital defects. This field holds the promise of regenerating damaged tissues and organs in the body by stimulating previously irreparable organs to heal themselves: repair of damaged heart muscle after a heart attack, replacement of skin for burn victims, restoration of movement after spinal cord injury, regeneration of pancreatic tissue to produce insulin for people with diabetes, and so forth. Regenerative medicine can improve the quality of life by supporting and activating the body's natural healing.

 Mesenchymal stem cells

Mesenchymal stem cells, shown by arrows, derived from umbilical cord blood. These cells will proliferate over time. Arrowheads point to round to triangular-shaped cells found in early culture that represent “contaminating” tissue cells. These cells will disappear with time.

What Are Stem Cells?

A stem cell is a "mother" cell that has the capacity for both replication and differentiation into other types of cells or tissues. Stem cells can be induced to become other cell types of the body.

As most people are aware, stem cells can be derived from embryos. This source for stem cells has been controversial because of ethical considerations and the accompanying heated public debate. However, there are other valuable sources for stem cells that do not present ethical conflicts. These sources include umbilical cord blood and placental tissues collected during or after birth and adult stem cells derived from different parts of the body such as bone marrow, blood, and fat.

Two types of stem cells are currently being evaluated for use in regenerative medicine: hematopoietic stem cells and mesenchymal stem cells. Hematopoietic stem cells are typically found in bone marrow and can be induced to become various types of blood cells. Mesenchymal stem cells are found in the bone marrow, fat, umbilical cord blood and tissue, and many other organs throughout the body. Of the two types of stem cells, mesenchymal stem cells currently offer the greatest potential for regenerative medicine in animals, particularly in horses, because they can differentiate into many different tissues and cells including bone, cartilage, tendon, and muscle.

Historical Perspective

The idea of transferring organs, cells, and tissues from one location to another began centuries ago as a primitive practice and has since evolved into a modern reality. Medical scientists have been developing this capability for hundreds of years, allowing modern medicine to triumph over countless challenges along the way to achieve the success of today. Much more work is needed to continue the progress.

Regenerative medicine using stem cells has its origins in bone marrow transplantation, in which stem cells repopulate the marrow of the recipient and become both blood and immunologically active cells. The first successful bone marrow transplant was performed by E. Donnall Thomas, MD, in 1956. He subsequently published a report of his work to describe how fairly large amounts of specially prepared marrow could be given intravenously without ill effect to the patient. He envisioned potential applications of marrow transplants for treating not only bone marrow diseases such as leukemia, but also victims of radiation accidents--a chilling premonition of the 1986 Chernobyl Nuclear Power Plant accident in the former Soviet Union.

Thomas found that bone marrow grafts could be obtained with circulating blood as well as bone marrow and that the cells responsible for recovery could be frozen and kept for long periods of time. He continued to work on developing techniques for successful bone marrow transplantation, including pioneering techniques to prevent rejection of the transplant by the body's immune system.

By the 1970s, the number of long-term survivors and the number of diseases that could be treated in this way increased so that it was possible to use the term "cured" for these patients. Thomas was one of two physicians awarded the 1990 Nobel Prize in Physiology or Medicine for this work in cell transplantation in the treatment of human disease. Today, bone marrow transplantation has progressed from a highly experimental procedure to being accepted as the preferred form of treatment for a wide variety of human diseases.

What This Means for Horses

Although regenerative medicine technology using stem cells for tissue repair and regeneration is just in its infancy, several current uses are becoming more popular and gaining acceptance within the equine industry. These applications are in the treatment of bone fractures and soft tissue injuries. As laboratory and clinical research provides new knowledge, we will have a better understanding of the potential of these cells for use in many other clinical disorders.

At UC Davis, we have assembled a team of 10 research scientists to work together over the next five years to develop stem cells for clinical applications in horses. In its first year, the Stem Cell Regenerative Medicine Group has developed methods of cell collection from different sources and techniques for harvesting, culturing and long-term storage of these cells. Ongoing work is focused on determining how to administer and monitor cells for appropriate treatment applications in the repair of bone, tendon and ligament injuries.

Tendon and ligament injuries in performance horses are the most common disorders currently being treated with stem cells in clinical trials--specifically, tendonitis of the superficial digital flexor tendon or "bowed tendon." One researcher has shown a lower recurrence rate of bowed tendons in racehorses treated with stem cells (18%) compared with traditional therapies (56%). Other tendon injuries that are being treated with increasing frequency are lesions of the deep digital flexor tendon that occur in the pastern region and within the hoof capsule.

Clinical trials with local stem cell injection are also being performed for treatment of suspensory ligament injuries of the fore and hind limbs. Because there is a low success rate using various treatment methods for lesions of the origin of the suspensory ligament in hind limbs, more and more horses are being treated with stem cell therapy. We expect that several published studies will soon be available to describe the effectiveness of stem cell therapy for treatment of suspensory ligament disorders. Anecdotally, the results have been promising.

Degenerative joint disease is a problem in performance horses and has great economic impact on the equine industry. Although there are many therapies to support joint health, the majority of these treatments are to relieve the symptoms at best. Stem cell therapy for joint disease is supported by original research performed in goats. It was shown in an arthritis model of the stifle that joints treated with stem cells had less arthritic changes compared with nontreated joints in the same animal. Several horses have been experimentally treated for joint injuries at UC Davis using stem cell therapy and the initial results have been positive. It is likely that results from clinical trials will soon be available to document the effectiveness of stem cells for joint disease.

 Tibial repair fail

This tibial fracture in an adult horse was successfully repaired initially, only to fail (shown) 5 weeks after the horse was standing comfortably in his stall. The horse had to be humanely destroyed after the implants failed before the bone could heal sufficiently enough to support the weight of the horse.

Fracture repair is an extremely challenging area of equine surgery. Many horses die of bone fractures due to the complexity of the injury and the inability to support the immense loads with current fixation equipment. Although bone grafts offer the advantage of containing live active cells that promote bone growth, there are several disadvantages. These include limited tissue availability, adverse effects on the patient's health caused when harvesting bone graft, potential graft rejection, and poor integration with native tissue.

One of the main challenges of bone repair in horses is the race between healing of the bone and either failure of implants (screws, plates) used for fixation or the development of laminitis in the opposite limb. Because horses cannot remain lying down for long periods of time, the horse will spend a good deal of time standing on three legs if the fourth is fractured. Unfortunately, if a horse does not bear weight evenly on all four legs, the legs that are not injured can suffer terrible inflammation and changes in blood flow. The condition known as laminitis can become so severe that the horse cannot be sustained, as was the case with Barbaro and other famous racehorses.

Even with advances such as specialized bone plates being made in internal fixation methods, the repair of long bone fractures in horses is extremely challenging. One of the main areas where stem cell therapy may be valuable for fracture treatment is to speed bone healing. The potential of stem cells to provide such an improved treatment represents a major breakthrough in veterinary medicine. At this point, an intense research program focusing on use of stem cells for bone healing is underway at UC Davis. The information that will come from this five-year program will direct future treatment of fractures in horses.

In addition to fracture repair, because of their robust bone-forming potential, stem cells might also be useful for regenerative therapies related to developmental bone disease. These conditions are commonly referred to as osteochondrosis (OCD) and have a tremendous economic impact on the equine industry. If a successful treatment for bone cysts could be developed using regenerative medicine technology, this would be one area where stem cells could produce a pronounced impact in both veterinary and human health. The UC Davis Stem Cell Regenerative Medicine Group is planning projects to investigate the use of stem cells for treating developmental bone disease during the upcoming year.

Research at UC Davis

Because mesenchymal stem cells currently offer the greatest potential for regenerative medicine in horses in their ability to differentiate into bone, cartilage, tendon and muscle cells, the UC Davis Stem Cell Regenerative Medicine Group has been working with these cells.

We recently developed a safe and easily accomplished method for collecting mesenchymal stem cells from umbilical cord blood and placental tissues during foaling. The process poses no threat to the health or safety of either the mare or foal. Once processed, these cells can be preserved by freezing and maintained for future use during the course of an individual animal's life. Current research also suggests that these placental-derived stem cells may have greater regenerative potential than cells derived from other tissue sources within the horse later in life. These cells may also be useful in treating disease among the parents and siblings within families of horses. These placental-derived stem cells represent an extremely valuable source of healing cell progenitors. Their collection and preservation at birth represent a sound strategy for maintaining future health and performance.

We have also found stem cells derived from bone marrow to be an excellent alternative source for therapeutic application. Bone marrow is easily extracted from the sternum of adult and juvenile horses. Recently, clinicians at the UC Davis School of Veterinary Medicine developed a new technique for harvesting bone-marrow-derived stem cells from the hip of horses less than 4 years of age. This method is most suitable for yearling horses because it yields a large quantity of high-quality marrow in a safe and painless manner.

 Uses of stem cells

Potential uses for stem cells in equine medicine.

Fat from the body of horses and other animals (including humans) is also a ready source for stem cells. Fat tissue can be surgically excised at any time during life and manipulated within the laboratory to harvest stem cells for immediate use or for culture, expansion, and storage for future use. These cells have been shown to have important therapeutic applicability and represent a valuable source of stem cells throughout the life of the patient.

Since stem cells are more potent in the younger animal, it would be beneficial to plan for the future and collect samples for stem cell culture and expansion early in the horse's life. For example, the collection and storage of bone marrow from horses under the age of 18 months is advantageous because it is well known and accepted by medical scientists that the quantity and quality of bone marrow-derived stem cells tend to decline with age. Therefore, if placental tissue stem cells have not been previously collected and stored, early collection and storage of bone marrow from valuable sport horse juveniles may prove to be a wise investment in the near future.

Banking cells is also recommended because it is likely that more than one treatment will be necessary for any given lesion as well as for future injuries that might occur while horses are actively training and competing.

There is still much to learn about stem cell therapy regarding treatment dose, timing, and frequency. It is difficult to derive a specific dose, but when treating various orthopedic disorders with pure populations of stem cells, anywhere between 5 and 10 million cells is currently being recommended. Based on research describing the anti-inflammatory effect and the ability of stem cells to orchestrate tissue repair and regeneration, early treatment should be beneficial. However, this will depend on the ability to bank stem cells and have a supply available immediately. Part of our research will be directed at development and refining methods to expand and store stem cells.

Because stem cells have the ability to target injuries and can help repair and regenerate damaged tissues, they may prove to be extremely valuable for treating many nonorthopedic disorders such as laminitis, exercise-induced pulmonary hemorrhage, left laryngeal hemiplegia, and neonatal maladjustment syndrome. As research advances in human medicine, disorders that are being evaluated for stem cell therapy in people will likely result in therapies for many equine diseases.

Regenerative medicine technology is advancing at an extremely fast pace for many different disorders in humans and animals. Stem cell therapy in horses offers great promise for tissue repair and regeneration of tendon and ligament injuries, bone fractures, and joint disease. Being prepared for the future by banking stem cells will help veterinarians provide state-of-the-art therapies for many equine diseases.

Excerpt from The Horse Report, Vol. 26, No. 4, October 2008, Center for Equine Health, School of Veterinary Medicine, University of California, Davis. For more information and articles see

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