Continuing our recent discussion of stem cell therapies for sports injuries, the use of mesanchysmal stem cells (MSCs) in orthopedic medicine can help in the repair of damaged tissue by harnessing the healing power of undifferentiated cells that form all other cells in our bodies. The process involves isolating these stem cells from a sample of your blood, bone marrow or adipose tissue (fat cells), and injecting it into the damaged body part to promote healing. Platelet-rich-plasma (PRP), a concentrated suspension of platelets (blood cells that cause clotting of blood) and growth factors, is also used to assist the process of repair.
Below are some examples of injuries and areas of research involving the use of mesenchymal stem cells (MSCs), which are (adult) tissue stem cells that are not only able to produce copies of themselves, but also able to divide and form bone, cartilage, muscle, and adipose (fat) stem cells when cultured under certain conditions:
Cartilage has long been considered as an ideal candidate for cell therapy as it is a relatively simple tissue, composed of one cell type, chondrocytes, and does not have a substantial blood-supply network. Of particular interest to researchers is repair of cartilage tissue in the knee, also called the meniscus of the knee. The meniscus is responsible for distributing the body’s weight at the knee joint when there is movement between the upper and lower leg. Only one third of meniscus cartilage has a blood supply, and as the blood supply allows healing factors and stem cells attached to the blood vessels (called perivascular stem cells) to access the damaged site, the meniscus’s natural lack of blood supply impairs healing of this tissue. Damage to this tissue is common in athletes, and is the target for surgery in 60 percent of patients undergoing knee operations, which usually involves the partial or complete removal of the meniscus, which can lead to long-term cartilage degeneration and osteoarthritis.
Recently, researchers increased their focus on the use of MSCs for treatment of cartilage damage in the knee. Some data from animal models suggest that damaged cartilage undergoes healing more efficiently when MSCs are injected into the injury, and this can be further enhanced if the MSCs are modified to produce growth factors associated with cartilage. It has been shown that once the MSCs are injected into the knee they attach themselves to the site of damage and begin to change into chondrocytes, promoting healing and repair. A small number of completed clinical trials in humans using MSCs to treat cartilage damage have reported some encouraging results, but these studies used very few patients, making it difficult to accurately interpret the results. There are currently a number of ongoing trials using larger groups of patients, and the hope is that these will provide more definite information about the role MSCs play in cartilage repair.
Tendinopathy relates to injuries that affect tendons – the long fibrous tissues that connect and transmit force from muscles to bones. Tendons become strained and damaged through repetitive use, making tendinopathy a common injury among athletes. Tendinopathy has been linked to 30 percent of all running-related injuries, and up to 40 percent of tennis players suffer from some form of elbow tendinopathy or “tennis elbow.” Damage occurs to the collagen fibers that make up the tendon, and this damage is repaired by the body through a process of inflammation and production of new fibers that fuse together with the undamaged tissue. However, this natural healing process can take up to a year to resolve, and results in the formation of a scar on the tendon tissue, reducing the tendon’s natural elasticity, decreasing the amount of energy the tissue can store and resulting in a weakening of tendon.
MSCs have the ability to generate cells called tenoblasts that mature into tenocytes. These tenocytes are responsible for producing collagen in tendons. This link between MSCs and collagen is the focus for researchers investigating how stem cells may help treat tendinopathy. Substantial research has been carried out on racehorses as they suffer from high rates of tendinopathy, and the injury is similar to that found in humans. Researchers discovered that by injecting MSCs isolated from an injured horse’s own bone marrow into the damaged tendon, recurrence rates were almost cut in half compared to horses that receive traditional medical management for this type of injury. A later study by the same group showed the MSCs improved repair, resulting in reduced stiffness of the tissue, decreased scarring and better fusion of the new fibers with the existing, undamaged tendon. It is not yet clear if these results are due to MSCs producing new tenocytes or their ability to modulate the environment around the tendinopathy, as described above. These promising results paved the way for the first pilot study in humans.
Bones are unique in that they have the ability to regenerate throughout life. Upon injury, such as a fracture, a series of events occur to initiate healing of the damaged bone. Initially there is inflammation at the site of injury, and a large number of signals are sent out. These signals attract MSCs, which begin to divide and increase their numbers. The MSCs then change into either chondrocytes, the cells responsible for making a type of cartilage scaffold, or osteoblasts, the cells that deposit the proteins and minerals that comprise the hard bone on to the cartilage. Finally these new structures are altered to restore shape and function to the repaired bone. A number of studies carried out in animals have demonstrated that direct injection or infusing the blood with MSCs can help heal fractures that previously failed to heal naturally. However, as was the case with tendinopathy, it is not yet clear if these external MSCs work by generating more bone-producing cells or through their ability to reduce inflammation and encourage restoration of the blood supply to injured bone, or both.
Brain injury in sports
There is mounting evidence that those taking part in sports where they are exposed to repetitive trauma to the head and brain are at a higher risk of developing neurodegenerative disorders, some of which are targets for stem cell treatments. For example, it has been reported that the rate of these diseases, like Alzheimer Disease, were almost four times higher in professional American football players compared to the general population. While the cause of this disease is not yet clear, it is associated with abnormal accumulation of proteins in neural cells that eventually undergo cell death and patients develop dementia. Researchers have attempted a number of strategies to investigate treatments of this disease in mice, including introducing neural stem cells that could produce healthy neurons. While some of these experiments have demonstrated positive, if limited, effects, to date there are no stem cell treatments available for Alzheimer’s Disease.
Boxers suffering from dementia pugilistica, a disease thought to result from damage to nerve cells, can also demonstrate some symptoms of Parkinson’s Disease (among others). In healthy brains, specialized nerve cells called dopaminergic neurons produce dopamine, a chemical that transmits signals to the part of the brain responsible for movement. The characteristic tremor and rigidity associated with Parkinson’s Disease is due to the loss of these dopaminergic neurons and the resulting loss of dopamine production. Researchers are able to use stem cells to generate dopaminergic neurons in the lab that are used to study the development and pathology of this disease. While a recent study reported that dopaminergic neurons derived from human embryonic stem cells improved some symptoms of the disease in mice and rats, stem cell based treatments are still in the development phase.