Little at that time last year, I didn’t know that animal stem cell therapy was a thing. Looking for a job that would capitalize on my biological background and love for animals, I found a position for a stem cell technician at a local veterinary office. I got the job! – and found that there are few things as exciting as changing a dog that was in so much pain that it could barely move, to become one who is able to frolic and that To enjoy life again.
Stem cell therapy is an effective tool for treating degenerative or other diseases as well as injuries. This is an effective way to use cells from the dog’s own body to regenerate damaged or diseased tissue. It was first used in the veterinary context in 2002 to repair tendons and ligaments in horses.1 Since severe leg injuries can be harmful to horses, especially those who practice racing and jumping, stem cell therapy has been a crucial factor. The results were remarkable – most of the horses treated were able to return to their previous activity.
Eventually, stem cell therapy has been used to treat pets, mostly for the same tendon or ligament repair problems, but has largely focused on arthritis. While stem cell therapy is not a panacea, it is a low-risk approach to treating injuries and degenerative diseases that provides our dogs with a better quality of life without drug dependence.
STEM CELL BASICS
What is a stem cell? It’s not quite as simple a question as it sounds. There are different types of stem cells, but the first main characteristic of a stem cell (SC) is that it can become one of several different cell types (called differentiation), creating different tissues. Stem cells are also very proliferative, which means they divide quickly and produce more cells, but at different rates depending on the type of SC.
There is a difference between embryonic and adult stem cells. Embryonic stem cells (ESCs) are responsible for embryonic development. They are pluripotent, which means that they can develop into any type of cell in the adult body. And they are very proliferative, more so than adult SCs. ESCs do not exist in the organism after birth.
An embryo develops from a single cell into a complex organism made up of several tissues. The course of development goes through many stages, but in short, some cells multiply and eventually develop into specialized cells that make up all of the different tissues in the body. ESCs in the early embryo multiply or divide to produce more cells very quickly. you are pluripotent, which means that they are able to become any type of cell in the organism. Eventually, as development proceeds, the cells become more specialized and less proliferative. There are many levels or levels as PCs move toward specialization.
At the beginning of development, ESCs differentiate into one of three germ layers, each of which gives rise to certain parts of the fetus. The endoderm (Endo = inner) many internal organs are formed, including the lungs, pancreas, stomach and liver. The mesoderm (Meso = Middle) bones, cartilage, tendons, ligaments, muscles, heart, fat and some nerve tissue are created. The ectoderm (ecto = external) neurons, outer layers of skin and hair are created. When ESCs share, they produce new SCs that specialize in one of these layers. These SCs produce more SCs as well as “progenitor cells”, the precursors for specialized cells that make up different tissues.
The Mesoderm Line produces mesenchymal stem cells (MSCs) that are used for therapy. The MSCs are taken into account multipotent (as opposed to pluripotent) because they can result in a limited number of tissues. MSCs and SCs from the other two lineages are present in the fully developed organism, but are dormant or inactive until needed. They are activated by injuries or illnesses and begin to multiply and differentiate.
PUTTING STEM CELLS INTO THERAPEUTIC WORK
There are many adult SCs in an adult organism. They are typically dormant and activated in response to tissue damage or disease, starting a complex cascade of cellular and chemical signals. The local SCs are activated and migrate to the specific area and multiply to produce more stem cells as well as progenitor cells to replace impaired specialized cells (such as cartilage or bone).
Importantly, MSCs can be used to treat tissues from which they do not arise. Their main function in these cases is to activate the SCs in that tissue. SCs also modulate the immune system and decrease the inflammatory response. The main function of the stem cells used for therapy is to regenerate healthy tissue directly (for tissues of the mesoderm line) or indirectly (for endoderm or ectoderm lines) to replace what is damaged or diseased.
In cases of arthritis or dysplasia where the bones or cartilage are damaged, the MSCs produce and become these cells. If the ligament is damaged, they produce ligament cells. In the cases of the other two lines, the MSCs stimulate the SCs on that line to produce new cells such as liver cells or skin cells. As the body regenerates new, healthy cells as a result, SC therapy is often referred to as regenerative medicine.
To do stem cell therapy, we must first extract the MSCs, concentrate them, and then bring them to the area of injury or disease. The closer the cells can be placed to the specific problem area, the better. In arthritis, the MSCs are injected into the diseased joint; MSCs are given intravenously for areas or organs where injection is not possible. As the SCs travel through the blood to reach various organs, they are available to respond to specific areas of stress in those tissues.
Most dogs receiving SC therapy will need multiple treatments. The time between treatments depends on the person. Repeated treatments are carried out at intervals of one to two months to a year. In my work I have seen a few cases where the problem has stopped after treatment. This is not common, but it does happen.
For SC therapy, MSCs are extracted from the body of the animal to be treated. They are found in tissues such as bones, fat, skin, brain, and heart.2 Initially, SCs were extracted from the bone marrow. However, there is a greater abundance of MSCs in adipose tissue and this tissue is less traumatic to harvest, so this is the most common source used.
There are several sources of adipose tissue in a dog. Some veterinarians ingest fat from the shoulder blade area. Others, including the veterinarian I work for, Dr. Robert Hagler of Lafayette, Calif., Prefer to use navel fat. This is a relatively simple procedure, but it requires general anesthesia.
Once removed, the fat is processed to extract the stem cells from the tissue (that’s my job!). The tissue goes through several mechanical and chemical digestion and separation steps. After a few hours, the exit is the stromal vascular fraction (SVF), which has concentrated mesenchymal SCs as well as other cells and components that support the action of the MSCs. Depending on the veterinarian, the SVF can be extracted on site. In this case, the dog will be treated on the same day (in the clinic where I work, the processing is done internally). The majority of vets send the fat off for processing and the SVF is sent back for treatment on the second day after harvest. At this point it is given to the dog.
Usually there are many cells from the fatty tissue for multiple treatments, depending on the condition being treated. The SVF required for initial treatment is slightly diluted in sterile saline and divided to account for the number of injections to be performed. Platelet rich plasma (PRP, more on this below) is usually added to the SVF to further support the stem cell response. We usually save a small portion of SVF to be given intravenously. Extra fat, containing cells for future treatments, is sent for processing and the cells are cryogenically frozen.
In most cases, the dog will be sedated for injection. If you’ve ever had an injection in a joint you know that these are quite painful and that it is much easier for the dog to be sedated. If MSCs are administered via IV only, sedation is usually not required. Once the injections are complete, the sedation will reverse and the dog can go home after a full recovery.
Future treatments are easier because fat and cell extraction is already complete. In our office, the dog comes to the office in the morning and has taken blood for PRP. The blood is processed to obtain the PRP, while thawed SVF goes through steps to wash and activate the MSCs. Once both components are made, they are administered as described above.
With joint injections, the first few days after treatment can be more painful than before treatment. The time it takes to see positive results varies from dog to dog. The average is a matter of weeks, but in some cases we’ve had positive results within a few days and sometimes it takes a month or two.
Many veterinarians accompany the MSCs with platelet-rich plasma. This substance amplifies the signals from the injured or damaged area and directs the MSCs to that area. It helps to get the most out of the MSCs in use. PRP also uses the dog’s tissue – in this case, blood drawn on the day of treatment. It is processed using a series of separation steps to concentrate platelets and a number of growth factors present in the blood, and then the PRP is activated. It is combined with the SVF and administered with it when injected.
In our office, we sometimes use PRP outside of SC therapy to promote healing. The most striking example of effectiveness I’ve seen was when two dogs had TPLO (Tibia Plateau Leveling Osteotomy) surgery for a broken ACL on the same day. Both had previously had TPLO surgery on the other hind leg. Upon completion of the procedure, PRP was administered to the surgical site. According to the owners and Dr. Hagler, both dogs had shorter recovery times compared to their previous surgeries and used the operating legs much earlier.
Stem cell therapy is very safe. The MSCs used for therapy are autologous, meaning they come from the same dog who will receive them, so there is no risk of rejection. There are essentially no side effects from the treatment itself. The treatment process is based on the animal’s biology using the natural healing powers of its own cells.
The greatest risk with therapy is general anesthesia, which is required to surgically remove some fat from the dog. There is always some risk involved in surgical procedures that require anesthesia, especially in older or frail dogs. In addition, there is some risk of infection as injections are often given into joints. To reduce this risk, injections of MSC are often accompanied by a small dose of antibiotic.
As mentioned earlier, SC therapy has been most commonly used in the treatment of arthritis and has resulted in significant improvements in pain levels, range of motion, and functional mobility. Our practice has also used it in many cases of hip or elbow dysplasia, with excellent results in very young dogs with severe dysplasia.
One example is Tugboat, a chocolate laboratory that was weakened by elbow dysplasia when it was only four months old. Its owner tried everything including costly surgery, pain medication, therapy, etc.
In search of other options, she decided on SC therapy. After treatment, Tugboat is a different dog! He used to find it hard to stand walking, but now he walks for over an hour a day and plays on the beach. He comes for repeated treatments about every six months if he shows signs of pain and reduced mobility and soon returns to normal activities.
MSCs are also used to treat damaged tendons and ligaments. SC therapy is helpful for partial tears, but not when the ligament is completely torn. There just isn’t enough material to bridge a full crack. In the clinic where I work, we have used SCs to treat degenerative myelopathy with good results. There were a number of small studies (n = 10 or less in most cases) that found that SC therapy improved the condition of dogs with arthritis, dysplasia, disc disease, perianal fistulas, inflammatory bowel disease, and keratoconjunctivitis sicca.3
Some dogs show improvement very early after treatment; others take longer and the degree of improvement varies. Dr. However, Hagler says, “I’ve never seen a dog that hasn’t improved.”
Overall the literature3 Agrees that SC therapy is effective, although many studies or reports are anecdotal based on practitioners’ data and experiences; Few clinical studies have been completed, although the companies whose technology will be used to extract the SCs have studies in the works.
THE FUTURE OF STEM CELL THERAPY
The exciting opportunities for future directions in stem cell therapy mainly concern the source of cells used to treat patients. Currently, the dog being treated must be the source of the cells used for treatment – otherwise the treatment would be legally considered a drug and must first be approved by the U.S. Food and Drug Administration (FDA).
A stem cell bank would be of great help in dogs lacking enough fat to harvest or in dogs too frail to undergo general anesthesia for surgical fat removal. Just as dogs can be universal blood recipients, they can also safely receive stem cells obtained from another dog. One study even found that MSCs can be extracted human Adipose tissue and transplanted into dogs.4th (Has anyone some fat you want to donate?)
Transplanting MSCs from another animal would be a game changer. There are cases when the dog with bank cells no longer needs them, either because they stopped therapy or because they passed away. It would be ideal if the dog’s owner could make the bank cells available to other dogs. This is not currently legal.
It is possible to grow MSCs (but not supporting cells) in a laboratory to increase their numbers and reduce the need to harvest fat more than once. A company is doing that now.
In some cases, SC therapy is contraindicated. Because of the proliferative and immunomodulatory effects of SCs, therapy should not be given in dogs known or suspected of having cancer. Dogs with an active infection should also not receive therapy.
SC therapy may also not be an option for dogs that are deficient in fat (until there is a stem cell bank for dogs!) Or for dogs that are too frail to withstand general anesthesia.
Stem cell therapy isn’t cheap; The cost of initial treatment, including harvesting fat, is near $ 2,500. Follow-up treatments can cost anywhere from $ 500 to $ 1,000. These numbers vary from vet to vet. The good news is that many pet insurance policies now cover SC therapy. Even without insurance, it’s much cheaper and less invasive than more drastic measures like joint replacements.
SC therapy is not a panacea and to achieve the greatest benefit requires basic, but sometimes overlooked, measures. It is important to support the health of the entire dog: keep its nails trimmed so that they do not interfere with walking. Feed them a good quality diet that supports overall health. Take precautionary measures to prevent infection after surgery. Keep up to date with follow-up treatments in a timely manner to minimize the dog’s pain or dysfunction. Supporting the general health of the dog and providing quality care are essential to get the most out of treatment.
Joanne Osburn is a stem cell technician at Mt. Diablo Veterinary Medical Center in Lafayette, CA. After spending nine years as a biology technician in a government laboratory, she is excited to work in the veterinary field where she can help improve the lives of pets. She lives in San Francisco Bay with her husband Paul and their super stupid dog Guster.