Stem cell therapy has gained much attention over the years through media and medical reporting.
Whether it is ground-breaking science in the generation of complete functional organs or the healing of spinal cord injuries, stem cells have remained at the forefront of the medical fields. The knowledge of these cells and their properties continues to grow and with that, new therapies and applications are becoming more readily available.
What are stem cells?
Stem cells may be classified into two groups based on their origin: embryonic and adult stem cells. For current veterinary use, we will focus on adult stem cells only. Adult stem cells are found in every tissue of the body including bone marrow, adipose tissue (fat), skin and the liver. These cells have the ability to differentiate into many types of tissue (pluripotent) under the appropriate circumstances and can additionally activate surrounding cells to aid in wound healing and tissue repair. Additionally, stem cells can also go through several cycles of cell division/ replication without differentiating into a specific tissue type i.e., they are self-replicating.
What is stem cell therapy?
Stem cell therapy is the process by which a tissue sample is obtained from the patient (either by fat or bone marrow extraction), and is then processed to isolate the stem cells, followed by administration back into the patient at the site of injury or disease by injection.
When stem cells are injected in a concentrated form, they act as a conductor for tissue repair by performing a number of tasks including:
- Differentiation into surrounding tissue type e.g. Chondrocytes to form new cartilage.
- Activation of surrounding resident stem cells
- Recruitment of other cell types, release of cytokines and growth factors to accelerate healing and tissue repair
- Regulation of inflammatory cytokines to reduce inflammation
- Stimulate new blood supply
- Protect cells from death
- Create a biological scaffold for healing tissues by forming extracellular matrix
- Reduction and/ or elimination of scar tissue/fibrosis.
- Immune modulation
What has stem cell therapy been used for?
In veterinary medicine, stem cell therapy has been used for a wide range of indications including:
- Degenerative Diseases
- Tendon injuries or tendinopathies
- Ligament Injuries
- Hip and elbow dysplasia
- Certain spinal conditions such as spondylosis, Lumbosacral disease and intervertebral disc disease.
- Fracture Repair
- Osteochondral Defects
- Organ dysfunction or failure e.g. Renal failure
- Auto-immune disease
Where are the cells obtained?
Adult-derived mesenchymal stem cells (ADMSCs) used in veterinary regenerative therapies are harvested from adipose tissue (fat) or bone marrow. Both types of mesenchymal stem cell are able to differentiate into cartilage, bone, tendons, ligaments for repair and regeneration. There is currently no evidence to suggest that one type is superior to the other for regenerative therapies.
Here at Greenside Veterinary Practice we can offer treatment with either culture expanded adipose derived mesenchymal stem cells (ADMSCs) or bone marrow aspirate concentrate (BMAC). The majority of cases are treated with ADMSCs due to the ease of harvest and the ability to culture expand and store cells for future use if required.
Bone marrow aspirate concentrate (BMAC)
BMAC is obtained under general anaesthesia from the femur via a sterile surgical procedure. A small incision is made in the skin and a long needle is inserted into the centre of the bone (medullary cavity) and the cells are aspirated with a syringe preloaded with an anticoagulant. The sample is then processed in house by filtration and centrifugation using specialist equipment to yield a cell fraction containing concentrated mesenchymal stem cells, platelets, and haematopoietic stem cells. This can then be injected into the affected area either alone or in combination with PRP and biological scaffolds during the same procedure/anaesthetic. BMAC is only suitable to treat two to three joints in total but we can culture expand these cells so that they can be stored for future use or used in more than three joints. A disadvantage of this method of collection is that patients can be painful following bone marrow harvest, but this can be minimised with an epidural anaesthetic prior to harvest and post-operative pain medications. Bone marrow harvest is considered more invasive than fat harvest.
Adipose derived mesenchymal stem cells (ADMSCs)
ADMSCs are harvested from fat taken from the inguinal fat pad in the groin or falciform ligament in the abdomen under general anaesthesia. Both sites require a small (2 cm) incision in the skin and there are no external sutures placed in the skin following harvest. A blood sample is also taken to provide serum which is used to culture the cells and provide a medium in which the stem cells are suspended when they are returned for injection. This ensures that only cells and fluids from the same animal are implanted and therefore there is no risk of rejection or reaction. The fat is processed and sent by overnight courier to an external laboratory that extracts the stem cells from the fat. These cells are then culture expanded in medium containing autologous serum. The culture process takes two to three weeks depending on the total number of cells required. Any number of stem cells can be cultured which is ideal if multiple joints are requiring treatment or large numbers of cells are required for intravenous or spinal injections.
ADMSCs are sterility tested and cryogenically frozen prior to shipping back to the practice. Implantation can then be arranged at any point as the frozen cells can be stored for an extended period of time (many years in fact!). A sample of the patients stem cells will be stored at the lab in case more cells are required in the future. These can then be used to culture more cells as required without having to undergo repeat fat harvest.
How are stem cells administered?
One of the most important aspects of SCT is the ability to get the cells to the target location. Treatment failures may result if the cells are not delivered correctly, and it is imperative that the injections are therefore performed by a suitably qualified vet trained using advance modalities.
At Greenside Veterinary practice injections are performed under sedation using ultrasound guidance for soft tissue injuries. Joint injections are performed by experienced vets and correct placement of the needle into the joint is ensured by aspirating joint fluid prior to injection. Spinal injections are assisted using radiography to determine correct placement of the needle into the target tissue if required. We have performed hundreds, if not thousands, of joint and spinal injections and you can rest assured that we are able to deliver regenerative therapies to their target location in every case.
For all intra-articular joint injections, joint fluid is removed prior to implantation. Arthritic joint fluid has been shown to be toxic to stem cells, so removal ensures the best survivability of the implanted cells. Removal of joint fluid also makes room for the administered treatment without causing excessive joint capsule distension following injection which can be associated with post implantation discomfort. We are currently exploring treatment protocols where the joint is pre-treated with PRP prior to treatment to change the environment within the joint to one that is more likely to ensure the survival of the implanted stem cells.
What Conditions can be treated?
Tendon and ligament injuries
Tendon and ligament injuries are very common in active dogs and can take a long time to heal due to poor blood supply. Conservative treatment allows for scar tissue formation which predisposes to reinjury or further degeneration resulting from decreased strength and flexibility. SCT heals the tendon or ligament injury through regeneration and elimination of fibrosis and scar tissue. Ultrasound guidance is used to target the stem cells directly into the site of injury and will also be used to monitor the repair process. Regenerative medicine is able to completely heal a tendon or ligament and with integrity uncompromised by scar tissue, patients are able to return to full activity and function.
Examples of commonly treated tendons and ligaments include:
- Supraspinatus tendon
- Biceps tendon
- Iliopsoas tendon
- Achilles tendon
- Carpal, tarsal and stifle collateral ligament
- Cranial cruciate ligament (partial tear)
For severe tendon and ligament injuries that have resulted in ruptures or complete tears, surgical intervention is required. However, injecting stem cells around the damage will result in regeneration of fibres rather than scar tissue formation which strengthens the repair.
Treatment of osteoarthritis (OA)
OA is a very common cause of pain and lameness in dogs and cats. OA is not just limited to older patients and we commonly she this condition in young animals as well as a result of hip or elbow dysplasia or trauma to the joint. OA is usually managed with painkillers (non-steroidal anti-inflammatories), joint supplements, weight management, and exercise modification. Physiotherapy and hydrotherapy are also important in maintaining muscle strength and fitness. Conservative management of OA often fails to provide a long-term response and once OA is present in a joint it continues to progress with time. Stem cell therapy provides another treatment option in the management of OA. Stem cell therapy has the potential to reverse or stop the inevitable degeneration that occurs once OA occurs in a joint and can be used at any stage in the disease process. Stem cells have a very potent anti-inflammatory effect when placed in an arthritic joint and they also have the potential to form new cartilage.
We have seen SCT remodel joints and remove arthritic bone resulting in increased range of motion and better functionality. In the majority of patients treated with SCT they are able to stop their pain killers and return to normal exercise for an extended period of time.
Spinal conditions such as lumbosacral (LS) disease, intervertebral disc disease and spondylosis, can cause chronic pain and dysfunction in dogs. Treatments options vary depending on the severity of the condition but include medical management, surgical intervention, physiotherapy, and laser therapy.
The use of stem cell therapy has recently been reported as a positive treatment option for spinal disease in dogs. At Greenside Veterinary practice we have pioneered a regenerative treatment option for lumbosacral disease. We have treated over 50 cases now with intravenous and epidural implantation of stem cells with a 100% success rate. LS disease is a chronically painful condition and can result in nerve dysfunction to the hind limbs, the bowels, and the bladder. Greenside Vets have recently published a small case series on LS disease.
Other conditions that have been treated with stem cell therapy at Greenside vets include:
- Renal failure
- Chronic nephritis
- Liver failure
- Liver cancer
- Auto-immune disease
- Lupoid onychodystrophy
- Skin defects
- Allergic skin disease
- Feline diabetes
- Feline gingivitis stomatitis complex
- Nerve damage
- Feline infectious peritonitis (FIP)
- Pulmonary Fibrosis
Following stem cell therapy, we recommend a course of laser therapy to commence immediately post implantation. Laser therapy energies the cells and stimulates the regenerative response through a process called photo biomodulation. Laser therapy also helps to reduce pain and inflammation associated with the joint injection until the stem cells can exert their anti-inflammatory and pain killing effects. We also recommend physiotherapy and hydrotherapy if appropriate to help the body adapt to the changes in function of the treated area and rebuild strength following periods of reduced use or compensation.
Stem cells can be stored for the lifetime of the animal in case a second treatment is required in the future. At Greenside vets we have a great success rate with stem cell therapy but in a few cases a second injection maybe required to complete the healing process. For the treatment of OA it is not uncommon for a patient to require a booster stem cell treatment 18 months to two years following the first treatment. This can easily be done by culturing more cells from cryopreserved samples without the need for repeat fat or bone marrow harvest.
SCT is a treatment option for any age or breed of dog or cat. The conditions listed above are just a few examples of the commonly performed treatments at Greenside Veterinary Practice. Many other conditions can potentially benefit from SCT and these can be discussed during consultation with Andy Armitage, our head of regenerative therapies. Before this type of treatment can be performed it is important to obtain a definitive diagnosis in order to target the treatment appropriately. We have a number of diagnostic aids which enable us to find the cause of the problem and then treat it with the most appropriate forms of regenerative medicine. Once a definitive diagnosis has been made then a detailed treatment protocol and an estimate of treatment costs will be provided by your regenerative medicine specialist. Response to treatment will be objectively assessed using appropriate tools to ensure your pet is progressing as expected following treatment.