Recently, the use of stem cells to promote healing and regeneration of certain tissues has become an emerging topic in veterinary medicine and surgery. Companies now exist that can process tissue harvested from a pet and provide the veterinarian with cells purported to have stem cell-like characteristics and may promote healing. However, myths and misinformation circulate about what stem cells actually are and what their utility is for veterinary applications. This brief paper will provide some information regarding the use of stem cells in veterinary medicine that may help clients, referring veterinarians and surgeons make decisions regarding their use based on current evidence as well as highlight what we still don’t know about this complex topic.
What are Mesenchymal Stem Cells (MSCs)?
Stem cells are self-renewing cells that are capable of differentiation into many different tissue types. They are often categorized based on their differentiation potential and their source.1 Totipotent stem cells can differentiate into all embryonic germ layers (endoderm, mesoderm, ectoderm) and can form a placenta.2 Pluripotent stem cells can differentiate into all the embryonic layers, but they are incapable of forming a placenta.2 Multipotent stem cells are generally considered committed to a specific embryonic layer (i.e. mesoderm), but they can differentiate into many different cell types (i.e. bone, cartilage, muscle, fat).2 Mesenchymal stem cells are considered multipotent stem cells, and they are often characterized in the literature by their ability to differentiate into bone, cartilage, and fat cells in vitro.2 These cells have been made to differentiate into many other tissue types in vitro, though, including muscle and nerve cells.1,3 Stem cells can come from an embryo (embryonic stem cells) or a post-natal animal (adult stem cells). An exciting recent finding is that mature cells can be reprogrammed to become pluripotent cells.4 These cells, termed induced pluripotent stem cells (iPS), are currently limited to the basic research setting. The stem cells used to treat canine orthopedic conditions are adult mesenchymal stem cells. These are most commonly obtained from either bone marrow (BM-MSCs) or fat tissue (AD-MSCs), but they can also be obtained from periosteum, synovium, muscle, and other sources.5
How are MSCs harvested?
The two sources of MSCs most commonly used in clinical veterinary medicine are bone marrow and adipose (fat) tissue. Bone marrow can be harvested from several different bones in a way similar to a bone marrow biopsy, which often requires general anesthesia. Only a small percentage (0.01 to 0.001 percent) of the cells collected are actually MSCs. Because of this, the sample of bone marrow is usually sent to a laboratory where the cells are amplified in culture. Once a sufficient number of MSCs are grown, the cells are sent back to the veterinarian to be administered to the patient. To harvest adipose tissue, a small surgical procedure is performed to remove approximately 50 grams of fat tissue. Many times the tissue needs to be sent off to a laboratory for processing (approximately three to four days), but some hospitals may have the capability of processing the tissue in-house (approximately four hours). The tissue processing produces what is called the stromal vascular fraction (AD-SVF). The SVF contains approximately 25-40 percent MSCs in addition to immune regulatory cells, anti-inflammatory macrophages, and other cells.6-9 Additionally, patient factors, such as age, and the harvest site have an impact on the number and characteristics of the cells.9,10 The advantage to using AD-SVF is the ease of harvesting large amounts of tissue and the short time for processing. However, this source of stem cells does not yield pure MSCs, and it is currently unknown what impact the remainder of the SVF has on healing in canine patients.
How do MSCs work and what can be treated with stem cells?
Stem cells exert their effect by two basic mechanisms: proliferation and differentiation into local cell types, and modulation of the local environment to promote proliferation and differentiation of resident cells.5 It is likely that MSCs work through a combination of these two mechanisms, and it has been suggested that their ability to modulate the local environment is the more important mechanism.11 In orthopedic patients, MSCs are most commonly used to treat tendon and ligament injuries and osteoarthritis, but their use is also advertised and suggested for fractures and other conditions.1,5,7,12 Despite the widely advertised and marketed benefits of MSCs for treating many canine orthopedic conditions, the evidence to support their use is both limited and not overly strong. For example, the ideal number and concentration of cells and frequency of injections needed are unknown and likely vary greatly between patients and disorders.5 In studies conducted by a company that processes stem cells, injection of AD-SVF into osteoarthritic joints (elbow and hip) improved subjective lameness scores.13,14 While these studies did document subjective improvement of lameness, they lack objective data and comparisons with any kind of control group comprised of other, less invasive treatments. Other studies investigating injection of AD-SVF into osteoarthritic joints have also shown improvement, but they also lack appropriate comparison or control groups.8,15 A case report of a dog with a chronic Achilles tendon injury treated with MSCs showed significantly improved clinical signs but incomplete ultrasonographic healing.16 While these reports suggest a promising role for stem cell therapy, additional blinded, controlled clinical studies are needed to increase our understanding of how to best use stem cells to treat canine orthopedic conditions.
In summary, stem cells show promise for treating a number of conditions. However, high level evidence for their use is severely lacking for canine patients, precluding the widespread recommendation for their use. The decision to use stem cells as a treatment should be made on a case-by-case basis after discussion between the veterinarian and client about the costs, risks, limited evidence, and other traditional treatments.
By Dr. Ryan E. McCally